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PubMed2005

ZDHHC8 as a candidate gene for schizophrenia: analysis of a putative functional intronic marker in case-control and family-based association studies.

BACKGROUND: The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. METHODS: Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186). RESULTS: In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity chi2 = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. CONCLUSION: The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.

Acyltransferases↗
PubMed2003

Novel system for the simultaneous analysis of geminivirus DNA replication and plant interactions in Nicotiana benthamiana.

The origin of replication of African cassava mosaic virus (ACMV) and a gene expression vector based on Potato virus X were exploited to devise an in planta system for functional analysis of the geminivirus replication-associated protein (Rep) in transgenic Nicotiana benthamiana line pOri-2. This line contains an integrated copy of a tandem repeat of the ACMV origin of replication flanking nonviral sequences that can be mobilized and replicated by Rep as an episomal replicon. A Rep-GFP fusion protein can also mobilize and amplify the replicon, facilitating Rep detection in planta. The activity of Rep and its mutants, Rep-mediated host response, and the correlation between Rep intracellular localization and biological functions could be effectively assessed by using this in planta system. Our results indicate that modification of amino acid residues R(2), R(5), R(7) and K(11) or H(56), L(57) and H(58) prevent Rep function in replication. This defect correlates with possible loss of Rep nuclear localization and inability to trigger the host defense mechanism resembling a hypersensitive response.

DNA Replication↗
PubMed1988

The relationship between airway responsiveness to histamine and pulmonary function level in a random population sample.

The association of nonspecific bronchial responsiveness (BR) with pulmonary function level has been studied in a random population sample of 2,156 male and female subjects 15 to 64 yr of age participating in the Vlagtwedde-Vlaardingen field survey on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. About 25% of the subjects responded with a decrease in baseline FEV1 of 10% or more after challenge with histamine in a concentration of 16 mg/ml or less inhaled over 30 s (PC10). In a stratified analysis, pulmonary function level appeared to be associated with BR in a dose-response relationship. The mean %FEV1 was consistently lower in the more responsive subjects. This relationship was confirmed in linear regression analyses, adjusting for age, sex, area of residence, and smoking habits. Exclusion of subjects with %FEV1 less than 80% diminished but did not change the association between FEV1 and BR. The magnitude of the effect of responsiveness on level of pulmonary function was considerable and statistically significant. In the subjects older than 21 yr of age, male responders (PC10 at less than or equal to 16 mg/ml) on average had an adjusted FEV1 of 32.5 centiliters less than nonresponders, and female responders had an adjusted FEV1 of 30.5 centiliters less (p less than 0.001). BR appeared to be an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette smoking. The effect of cigarette smoking on pulmonary function level in this population sample was significant only in men older than 21 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2025

Integrated proteomic network analysis reveals PTPRC as a central hub protein orchestrating co-expression modules and metabolic dysregulation in renal carcinoma: PTPRC protein molecular action.

The occurrence of renal carcinoma is closely related to a variety of molecular mechanisms and metabolic disorders. PTPRC (protein tyrosine phosphatase receptor C), as an important regulatory protein, was studied to reveal the role of PTPRC in renal carcinoma through comprehensive proteomic network analysis, especially its core position in the coordination of co-expression modules and metabolic disorders. This study was the first to download and process multiple publicly available renal cancer transcriptome data to conduct differential gene expression analysis across datasets. Functional enrichment and disease ontology analysis were performed on the transcriptome of renal cancer, and weighted gene co-expression network (WGCNA) was constructed. The results showed that comprehensive principal component analysis revealed significant differences in the transcriptome of renal cancer, and functional annotation revealed specific pathways associated with renal cancer. WGCNA analysis identified tumor-associated co-expression modules, while multi-omics analysis further identified core regulatory networks including PTPRC. As a central hub protein, PTPRC plays an important coordinating role in the co-expression module and metabolic dysregulation of renal carcinoma. This discovery provides a new perspective for understanding the molecular mechanism of kidney cancer.

Humans↗
PubMed2005

Gender and family composition related to discharge destination and length of hospital stay after acute stroke.

Informal care by family members still plays an important role in home care after acute stroke. This study determined the clinical and demographic factors, such as family structure, that predict discharge to home and length of hospital stay (LOS) after acute stroke hospitalization. We reviewed the sex, age, family structure before stroke, type of stroke, size of the lesion, activities of daily living (ADL) function at discharge, discharge destination, and LOS of stroke patients (114 cerebral infarctions and 44 intracerebral hemorrhages) admitted to a neurosurgical hospital. Patients with cerebral infarction were older than those with intracerebral hemorrhage (median 75 vs 66 years). Ninety-eight were discharged to home (62%). In the logistic regression analysis, low ADL function, medium or large infarction, and intracerebral hemorrhage (vs lacunar infarction) were significantly associated with discharge to a destination other than home. Of the patients discharged home, low ADL function was strongly associated with LOS in the multiple regression analysis. In addition, living with a spouse only had the opposite effect on LOS in men and women (p=0.050 and 0.071, respectively). LOS tended to be shorter for men with a wife, but longer for women with a husband. The structure and gender roles in a stroke patient's household may need further attention for the efficient use of hospital resources.

Acute Disease↗
PubMed2002

The relationship of perceived self-efficacy to quality of life in chronic obstructive pulmonary disease.

From a biomedical perspective, variations in the quality of life of chronic obstructive pulmonary disease (COPD) patients may be attributed to changes in pulmonary function; thus, an increase in lung function should be correlated with an increased score on a health-related quality-of-life measure. However, inconsistent results regarding correlations between various measures of pulmonary function and quality of life have been reported in the literature. The authors evaluated a social cognitive model of quality of life among persons with COPD by analyzing relationships among biomedical measures, self-efficacy measures, and quality-of-life measures in a recursive path model. Path analysis results indicated that the association of pulmonary function and symptoms with quality of life was mediated by perceived self-efficacy for functional activities.

Activities of Daily Living↗
PubMed2002

What's in the 'BAG'?--A functional domain analysis of the BAG-family proteins.

Bcl-2-associated athanogene (BAG)-family proteins are BAG domain-containing proteins that interact with the heat shock proteins 70, both constitutive Hsc70 and inducible Hsp70. BAG-family proteins bind through the BAG domain to the ATPase domain of Hsc70/Hsp70. The BAG domain, approximately 110 amino acids in length, is a conserved region at the carboxyl terminus and consists of three anti-parallel alpha helices based on X-ray crystallography and NMR studies. The second and third alpha-helices of the BAG domain interact with the ATP-binding pocket of Hsc70/Hsp70. Currently, six human BAG proteins have been reported, four of which have been shown to functionally bind Hsc70/Hsp70. BAG-family proteins regulate chaperone protein activities through their interaction with Hsc70/Hsp70. Over-expression of BAG-family proteins is found in several cancers and has been demonstrated in the laboratory to enhance cell survival and proliferation. The anti-apoptotic activities of BAG-family proteins may be dependent on their interactions with Hsc70/Hsp70 and/or binding to Bcl-2. Both BAG-1 and BAG-3/CAIR-1 interact with Bcl-2 and have been shown to have a supra-additive anti-apoptotic effect with Bcl-2. Several N-terminal domains or motifs have been identified in BAG-family proteins as well. These domains enable BAG-family proteins to partner with other proteins and potentially alter the activity of those target proteins by recruiting Hsc70/Hsp70. BAG-family proteins participate in a wide variety of cellular processes including cell survival (stress response), proliferation, migration and apoptosis.

Amino Acid Sequence↗
PubMed1988

T11/CD2 activation of cloned human natural killer cells results in increased conjugate formation and exocytosis of cytolytic granules.

The T11 (CD2) antigen has been found to be an alternate pathway for antigen-independent activation of resting T cells. T11 triggering also results in activation of NK cells and enhancement of their cytolytic function. The present studies were carried out to further define the mechanisms whereby cytotoxicity is enhanced after T11 activation. A series of clonal human NK cell lines were analyzed after incubation with monoclonal anti-T112 and anti-T113 antibodies specific for different epitopes of the CD2 protein. Anti-T112/3 triggering resulted in increased cytotoxicity against a variety of target cells. Similar results were obtained with F(ab')2 fragments of anti-T112/3, indicating that this effect was not mediated through binding of FcR. The induction of cytotoxicity was found to be associated with increased formation of effector cell-target cell conjugates and with release of secretory granule-localized 35S-labeled proteoglycans. Both enhanced conjugate formation and cytotoxicity could be blocked by anti-lymphocyte function-associated antigen (LFA-1) mAb. Ultrastructural analysis of NK cells after T11 activation demonstrated increased adherence of effector cells to targets and other NK cells as well as a directional reorientation of cytoplasm and intracellular granules toward the area of contact between cells. Discharge of granules occurred into pockets bounded by closely apposed plasma membranes. In the presence of anti-LFA-1 and anti-T112/3, the close apposition and formation of pockets between effector cells and target cells did not occur but the cells exocytosed their intracellular granules. T11 activation of NK cloned cells also resulted in the formation of the homotypic conjugates and autocytotoxicity. As seen with resistant allogeneic targets, autocytotoxicity was mediated by F(ab')2 fragments of T112/3 antibodies and could be blocked by anti-LFA-1 antibody. Ultrastructural analysis of NK cloned cells after T11 activation confirmed the presence of homotypic conjugates with reorientation of effector cells toward one another and discharge of cytolytic granules into pockets formed between NK cloned cells. Taken together, these results indicate that T11-induced cytolytic function of NK cells is, in part, mediated through increased binding of effector cells and targets and that enhanced conjugate formation is at least in part mediated by the LFA-1 antigen. In addition, T11 activation results in the triggering of the cytolytic mechanism of NK cells and the exocytosis of cytolytic granules and their constituents.

Antibodies, Monoclonal↗
PubMed2006

Evaluation of the role of Finnish ataxia-telangiectasia mutations in hereditary predisposition to breast cancer.

Biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene result in ataxia-telangiectasia (A-T). Studies on A-T families have shown that obligate female carriers have increased risk of developing breast cancer. Here we have evaluated the role of known Finnish ATM germ line mutations as possible breast cancer predisposing alleles outside A-T families by analyzing their prevalence in large cohorts of familial and unselected breast cancer cases. Of seven different alterations, two were observed in the studied breast cancer material. ATM 6903insA (causing protein truncation) was seen in 3/541 familial and 5/1124 unselected cases, but not among healthy population controls (0/1107). 7570G>C (Ala2524Pro) occurred in 1/541 familial and 2/1124 unselected cases compared with 1/1107 in controls. Additionally, 8734A>G (Arg2912Gly) associated previously with breast cancer susceptibility and suggested to be causative also for A-T was detected in 2/541 of familial cases, but not in unselected cases (0/1124) or controls (0/1107). In total, heterozygous ATM mutation carriers were observed in 6/541 familial [P = 0.006, odds ratio (OR) 12.4, 95% confidence interval (CI) 1.5-103.3) and 7/1124 unselected cases (P = 0.07, OR 6.9, 95% CI 0.9-56.4), compared with 1/1107 in controls, suggesting an apparent yet overall limited contribution to predisposition to cancer. The current results also provided evidence for founder effects in the geographical distribution of these mutations. Interestingly, results from functional analysis of the breast cancer-associated ATM mutations indicated that cancer susceptibility is not restricted to mutations with dominant-negative effect on kinase activity, displayed only by 7570G>C, whereas 8734A>G showed only a partial defect in the phosphorylation of ATM substrates, and 6903insA seemed to be a null allele.

Ataxia Telangiectasia↗
PubMed2000

Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas.

Loss of function of the tumor suppressor gene p53, increased expression of glutathione-S-transferase pi (GST7pi) and the major vault protein are involved in drug resistance of ovarian carcinomas. However, a study comparing these factors has not yet been performed. Therefore, paraffin-embedded material of 213 ovarian tumors with well-documented follow-up was used for immunohistochemical analysis of p53 protein, GSTpi, and major vault protein (antibodies LRP-56, LMR-5). Forty-six percent of the cases showed nuclear p53 accumulation. Strong immunoreactivity for GSTpi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, respectively. p53 positivity was most often found in serous carcinomas (p < 0.05). Strong GSTpi expression was the only factor that correlated with clinical resistance to chemotherapy (p = 0.04). In the whole group, as well as in FIGO III cases stratified for residual disease < or = and >2 cm, p53 and GSTpi correlated with an adverse outcome (p = 0.01 for p53 and p = 0.04 for GSTpi). Strong LRP-56 or LMR-5 staining was associated with a tendency towards poorer prognosis, without reaching statistical significance. In multivariate analysis for FIGO III, only residual disease and p53 proved to be independent prognostic factors. Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug resistance.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

[Functional recovery in post-acute rehabilitation: patient characteristics and treatment effect].

OBJECTIVE: Most studies on the effectiveness of rehabilitation consider only particular rehabilitation treatments for particular conditions, and do not give a global vision of the issue. This study evaluated the effectiveness of various types of post acute rehabilitative care in patients with different diagnoses by investigating the association between treatments and functional gain by type of impairment and severity on admission. DESIGN, SETTING AND PARTICIPANTS: Information on the characteristics of patients and the rehabilitative treatments was collected using an Italian version of the Minimum Data Set-Post Acute Care. The questionnaire was created and validated by the Centers for Medicare and Medicaid Services, it is divided in various section and was filled in at regular intervals throughout the hospital stay. Patients included in the study were 1918. MAIN OUTCOME MEASURES: We used factor analysis to summarize each section in a single continuous variable. The observed functional gain was calculated as the difference between functional status at the beginning and at the end of the admission. A multiple linear regression analysis was performed to evaluate the association between rehabilitation treatments and functional gain, adjusting for patient characteristics and severity at admission. The effectiveness of the treatments were obtained by calculating the difference between the overall functional gain of the hospital stay and the predicted functional gain of the stay in the absence of rehabilitation treatments. RESULTS AND CONCLUSION: The effectiveness of treatments differs across diagnostic class and it is associated directly with severity of functional status at admission. In most cases, the positive effect of treatments combines with the spontaneous functional gain; in other cases the positive effect of treatments opposes the spontaneous deterioration of patient functional status.

Comorbidity↗
PubMed2026

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5&#xa0;&#xb1;&#xa0;13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p&#xa0;=&#xa0;0.0002, I2&#xa0;=&#xa0;0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

Humans↗
PubMed2001

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

Adult↗
PubMed1997

Neuropeptide amidation in Drosophila: separate genes encode the two enzymes catalyzing amidation.

In vertebrates, the two-step peptide alpha-amidation reaction is catalyzed sequentially by two enzymatic activities contained within one bifunctional enzyme called PAM (peptidylglycine alpha-amidating mono-oxygenase). Drosophila head extracts contained both of these PAM-related enzyme activities: a mono-oxygenase (PHM) and a lyase (PAL). However, no bifunctional PAM protein was detected. We identified cDNAs encoding an active mono-oxygenase that is highly homologous to mammalian PHM. PHM-like immunoreactivity was found within diverse larval tissues, including the CNS, endocrine glands, and gut epithelium. Northern and Western blot analyses demonstrate RNA and protein species corresponding to the cloned PHM, but not to a bifunctional PAM, leading us to predict the existence of separate PHM and PAL genes in Drosophila. The Drosophila PHM gene displays an organization of exons that is highly similar to the PHM-encoding portion of the rat PAM gene. Genetic analysis was consistent with the prediction of separate PHM and PAL gene functions in Drosophila: a P element insertion line containing a transposon within the PHM transcription unit displayed strikingly lower PHM enzyme levels, whereas PAL levels were increased slightly. The lethal phenotype displayed by the dPHM P element insertion indicates a widespread essential function. Reversion analysis indicated that the lethality associated with the insertion chromosome likely is attributable to the P element insertion. These combined data indicate a fundamental evolutionary divergence in the genes coding for critical neurotransmitter biosynthetic enzymes: in Drosophila, the two enzyme activities of PAM are encoded by separate genes.

Amides↗
PubMed1997

Long-term results of surgery for active infective endocarditis.

OBJECTIVE: This paper was undertaken to determine the long-term outcome of active infective endocarditis treated with antibiotic and radical excision of infected tissues by surgery. METHODS: From October 1978 to August 1994, 122 consecutive patients were operated on during the acute phase of infective endocarditis. There were 85 men and 37 women whose mean age was 50 years, ranging from 20 to 79. Surgery was needed because of one or more of the following complications: cardiogenic/septic shock in 19 patients, congestive heart failure in 68, persistent sepsis in 64, peripheral embolization in 20, and cerebral embolization in 10. The offending microorganism was identified in 110 patients, staphylococci were the most common ones. Seventy-six patients had native valve endocarditis and 46 had prosthetic valve endocarditis. Simple valve replacement or repair was performed in 60 patients and radical resection of the valve and surrounding tissues with reconstruction of the heart with either fresh autologous pericardium or glutaraldehyde-fixed bovine pericardium was performed in 62 with paravalvular abscess. Pulmonary autograft and aortic homograft were used in only three patients, the remaining patients had either bioprostheses or mechanical heart valves if valve repair was not feasible. RESULTS: There were nine deaths, for an operative mortality of 7.4%. Logistic regression analysis identified preoperative shock and renal failure as predictors of operative mortality. Operative survivors were followed up from 4 to 173 months, mean of 56.4. The actuarial survival at 10 years was 61 +/- 6%. Logistic regression analysis identified preoperative New York Heart Association functional class IV and perioperative renal failure as predictors of late mortality. Eight patients developed recurrent endocarditis 10-102 months postoperatively. The freedom from recurrent endocarditis at 10 years was 79 +/- 9%. All patients who developed this late complication had paravalvular abscess at the time of original operation. CONCLUSIONS: These data suggest that surgery for active infective endocarditis yield a high probability of eradicating the infection with relatively low operative mortality and good long-term results.

Abscess↗
PubMed2001

Processability of cottonseed proteins into biodegradable materials.

The manufacture of biodegradable materials from agricultural sources is a real challenge, because of environmental concerns and the need to make full use of resources. Cottonseed is an important protein source that could be used in nonfood applications, as a substitute for synthetic polymers. For the first time, the viscoelastic behavior of cottonseed protein isolate (CPI), plasticized with glycerol, was characterized in order to determine the temperature range within which cottonseed protein-based materials can be formed by extrusion or thermomolding. Research involved three main techniques: dynamic mechanical analysis to study the alpha protein relaxation associated with glass transition, as a function of plasticization by glycerol; DSC analysis to determine the effect of glycerol content on the protein denaturation and degradation temperatures; and ATG-TG/FTIR to characterize the protein degradation. The results indicated that cottonseed proteins are thermoplastics with a T(g) ranging from 80 to 200 degrees C when the glycerol content varies from 0% to 40% (w/w, dry basis). The proteins' thermal denaturation temperature increased from 141 (without glycerol) to 195 degrees C in the presence of 40% (w/w) glycerol. Protein degradation occurred at 230 degrees C irrespective of glycerol content, with the release of a variety of compounds. Glycerol acts as a plasticizer and thermal stabilizer of the proteins and increases the range of temperatures (80-175 degrees C) at which the material can be processed.

Biodegradation, Environmental↗
PubMed1995

Characterization of essential domains for the functionality of the MHBst transcriptional activator and identification of a minimal MHBst activator.

Integrated hepatitis B virus DNA derived from hepatocellular carcinomas can express, in one third of the cases investigated so far, a transcriptional activator encoded from 3' terminal truncated surface (preS/S) genes resulting in a C-terminally truncated middle surface protein (MHBst). Since MHBst, in contrast to the secreted MHBs, is retained in the secretory pathway at the ER, the question as to whether the retention generates the transcriptional activator function was investigated. Through fusion of MHBs to the ER-retention signal KDEL, it was shown that the intracellular retention does not generate the transcriptional activator function. Tryptic digestions of microsomal vesicles revealed that the amino terminal domain of MHBst directs into the cytoplasmic compartment, whereas in MHBs this domain directs into the lumen of the ER. This structural difference appears to be why transcriptional activator function arises. Through deletion analysis it was shown that non-membrane-associated MHBst proteins are also functional activators. Nonmembrane associated MHBst proteins represent a second class of MHBst proteins. These MHBst-proteins are homogenously distributed all over the cell and show no difference in functionality as compared to the membrane-associated MHBst proteins. MHBst53 (truncated at aa53) was shown to be a minimal activator of this class. Both classes of MHBst proteins were found to form dimers; an which is involved in mediating the dimerization. The integrity of this domain was also revealed to be a prerequisite for the functionality of the activator, suggesting a linkage between dimerization and functionality.

Animals↗