Biomedical subjects

K L Jang

Publications and source records attributed to K L Jang.

44 records · Page 3Linked to original sources

PubMed1995

Human foamy virus Bel1 transactivator contains a bipartite nuclear localization determinant which is sensitive to protein context and triple multimerization domains.

The Bel1 protein of human foamy virus is a 300-amino-acid nuclear regulatory protein which transactivates the gene expression directed by the homologous long terminal repeat and the human immunodeficiency virus type 1 long terminal repeat. While previous reports suggested that the single basic domain of Bel1 from residues 211 to 222 and/or 209 to 226 is necessary and sufficient for efficient nuclear localization (L. K. Venkatesh, C. Yang, P. A. Theodorakis, and G. Chinnandurai, J. Virol. 67:161-169, 1993; F. He, J. D. Sun, E. D. Garrett, and B. R. Cullen, J. Virol. 67:1896-1904, 1993), our recent data showed that another basic domain, from amino acid residues 199 to 200, is also required for nuclear localization of Bel1 (C. W. Lee, C. Jun, K. J. Lee, and Y. C. Sung, J. Virol. 68:2708-2719, 1994). To clarify this discrepancy, we constructed various bel1-lacZ chimeric constructs and several linker insertion mutants and determined their subcellular localization. When the region of Bel1 containing basic domains was placed at an internal site of the lacZ gene, the nuclear localization signal (NLS) of Bel1 consisted of two discontinuous basic regions separated by an intervening sequence. Moreover, insertion of specific amino acids between two basic regions disrupted the activity of the Bel1 NLS. On the other hand, Bel1 residues 199 and 200 were not required to direct the Bel1-beta-galactosidase chimeric protein to the nucleus when the Bel1 NLS was appended to the amino terminus of beta-galactosidase. These results indicate that the function of the Bel1 NLS is sensitive to the protein context within which the sequence is present. In addition, we demonstrated that the Bel1 protein forms a multimeric complex in the nuclei of mammalian cells by using a sensitive in vivo protein-protein interaction assay. Mutational analyses revealed that the regions which mediate multimer formation map to three domains of Bel1, i.e., residues 1 to 31, 42 to 82, and 82 to 111. Furthermore, our results show that the region of Bel1 from residues 202 to 226 prevents Bel1 from forming a multimeric complex.

Amino Acid Sequence↗

PubMed1994

Categorical distinctions in the study of personality disorder: implications for classification.

This article discusses the historical underpinnings of psychiatric classification and examines empirical evidence relevant to (a) whether personality disorders are distinct from each other and from normal personality and (b) whether personality disorders should be classified separately from other mental disorders. At the phenotypic level, research evidence strongly supports the use of a dimensional model to delineate personality disorders; evidence about their genotypic representation is less conclusive though still supportive. Neither empirical nor rational arguments indicate strong justification for separating personality disorders from other mental disorders, as has been done in both the third and fourth editions of the Diagnostic and Statistical Manual of Mental Disorders. Distinctions between abnormal and disordered personality are considered, and suggestions are made for more satisfactory diagnostic classificatory schemes.

Comorbidity↗

PubMed1993

Genetic and environmental contributions to dimensions of personality disorder.

OBJECTIVE: The authors estimated the heritability of the basic dimensions of personality disorder and the relative proportions of the variance attributable to genetic and environmental sources. METHOD: The subjects were 175 volunteer twin pairs (90 monozygotic and 85 dizygotic) from the general population. Each twin completed the Dimensional Assessment of Personality Pathology, a questionnaire that assesses 18 dimensions of personality disorder. The questionnaire was developed on the basis of factor analytic studies that identified a stable structure underlying personality disorders in clinical and nonclinical subjects. Structural equation model-fitting methods were used to estimate the influence of additive genetic, common environmental, and unique environmental effects. RESULTS: The estimates of broad heritability ranged from 0%, for conduct problems, to 64%, for narcissism. Behaviors associated with submissiveness and attachment problems had low heritability. For most dimensions, the best-fitting model was one that specified additive genetic and unique environmental effects. CONCLUSIONS: These results are similar to those reported for normal personality and suggest a continuity between normal and disordered personality.

Adolescent↗

PubMed1992

The herpes simplex virus immediate-early protein ICP27 stimulates the transcription of cellular Alu repeated sequences by increasing the activity of transcription factor TFIIIC.

Infection with herpes simplex virus (HSV) results in an increase in the transcription of the endogenous Alu repeated sequence by RNA polymerase III. This effect is also observed in uninfected cells stably transformed with a plasmid expressing the HSV immediate-early protein ICP27 or in cells transfected with the gene encoding this protein. Both uninfected cells expressing ICP27 and cells infected with virus producing functional ICP27 display increased activity of the cellular transcription factor TFIIIC when compared with untreated cells. This increase is not observed, however, in cells infected with a mutant strain of virus which does not produce ICP27. Hence ICP27 induces elevated Alu transcription by activating transcription factor TFIIIC, which is the limiting factor for such transcription. This is the first report of increased activity of a cellular transcription factor during HSV infection, when most cellular gene activity is inhibited.

Animals↗

PubMed1992

The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC.

The HIV Tat protein is able to upregulate the transcription by RNA polymerase III of cotransfected or endogenous cellular Alu-repeated sequences in both HeLa and Jurkat T cells. This effect is mediated by an increase in the activity of transcription factor TFIIIC, which binds to the B box in the RNA polymerase III Alu promoter. This is the first example of an effect of the Tat protein on the transcription of a cellular gene or on the activity of a cellular transcription factor. The significance of this effect for the life cycle of HIV and its interaction with infected cells is discussed.

Actins↗

PubMed1991

Activation of the cellular transcription factor AP-1 in herpes simplex virus infected cells is dependent on the viral immediate-early protein ICPO.

Lytic infection with herpes simplex virus (HSV) results in the repression of most host cell protein synthesis but produces an increased activity of the cellular AP-1 transcription factor. This increase is paralleled by an increase in the transcription rate of the proto-oncogene encoding the AP-1 component, c-Jun resulting in an increase in c-Jun protein in infected cells. The increased AP-1 activity in infected cells is dependent upon the HSV immediate-early protein ICPO. Thus a mutant lacking the gene encoding this protein fails to increase AP-1 activity whilst an ICPO expression plasmid can specifically increase the activity of an AP-1 dependent promoter in co-transfection experiments. The implications of these effects in the interaction of HSV with cultured cells are discussed.

Binding Sites↗

PubMed1989

HSV infection induces increased transcription of Alu repeated sequences by RNA polymerase III.

The Alu family of repeated sequences is transcribed by both RNA polymerase II and RNA polymerase III. In cells infected with HSV, transcription by polymerase III increases while transcription by polymerase II decreases. By using virus strains carrying mutations in the genes encoding individual regulatory proteins, we have shown that this effect is dependent upon the immediate-early protein ICP27 and occurs by a process distinct from those which regulate viral gene expression. This is the first example of increased transcription of endogenous cellular sequences by RNA polymerase III during infection with a DNA virus.

Cell Nucleus↗

PubMedDate not supplied

Gender differences in the etiology of anxiety sensitivity: a twin study.

OBJECTIVE: To estimate the magnitude of genetic and environmental factors on anxiety sensitivity by gender. DESIGN: Classic twins reared-together study design. PATIENTS: A community sample of 337 twin pairs, including 179 monozygotic (45 brother and 134 sister pairs) and 158 dizygotic (28 brother, 94 sister, and 36 brother-sister pairs). METHOD: Twin pairs completed the Anxiety Sensitivity Index (ASI) using a postal survey design. The ASI is composed of three factors: (1) fear of anxiety-related somatic sensations; (2) fear of cognitive dyscontrol due to beliefs that sensations like depersonalization are signs of mental illness (e.g., fear of concentration problems); and (3) fear of publicly observable anxiety reactions (e.g., fear of trembling). Biometrical modeling techniques were used to estimate heritability of the ASI dimensions by gender. RESULTS: ASI factors are heritable only in women, accounting for 37% to 48% of the total variance (median, 44.5%). Environmental factors accounted for all the variability in men. CONCLUSIONS: These findings have implications for understanding the etiology of panic disorder. Previous research suggests that anxiety sensitivity is a risk factor or diathesis for this disorder, and that panic disorder is more prevalent in women than men. Our findings suggest the hypothesis that the increased prevalence in women may occur because anxiety sensitivity is heritable in women.

Anxiety↗