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At least 19 recordsLinked to original sources
PubMed2026

p27 Expression in Wild-Type KRAS Colon Cancer.

p27, a cyclin-dependent kinase inhibitor, functions as a tumour suppressor in the nucleus but may acquire oncogenic properties when mislocalized to the cytoplasm. While KRAS mutations can induce p27 phosphorylation and cytoplasmic retention, the regulation and significance of p27 expression in wild-type (WT) KRAS colorectal cancer (CRC) remain unclear. This study investigated the relationship between WT KRAS status and p27 localization, as well as the potential roles of miR-221/222 expression and the CDKN1B V109G polymorphism in CRC susceptibility. Immunohistochemical analysis of 50 WT KRAS CRCs and adjacent normal tissues revealed the highest percentage of p27-positive cells in the superficial layer of normal mucosa and significantly fewer in the tumour center. WT KRAS tumours with KRAS expression showed increased p27 expression and predominant cytoplasmic localization at the invasive front, suggesting altered p27 subcellular distribution. miR-221/222 expression showed no correlation with p27 levels, and the CDKN1B V109G polymorphism was not associated with CRC risk. This study is the first to examine p27 localization in WT KRAS CRC. The observed association between WT KRAS expression and cytoplasmic p27 localization highlights a potential mechanism contributing to tumour progression through altered p27 function.

Humans↗
PubMed1991

An antigenic determinant is shared by psoriasis-associated p27 antigen and the Fc part of human IgG.

Rabbit antisera against the major internal protein, p27, of retrovirus-like particles from psoriatic urine, and against the serologically cross-reacting antigen, pso p27, from psoriatic scale, reacted with the Fc part of human IgG. Evidence indicating that the p27 antigen and the pso p27 antigen are identical has been presented in previous reports. A commercial antiserum against human IgG recognized a component in the pso p27-containing solution used as the source of antigen for immunization of the rabbits. By means of monoclonal antibodies against the pso p27 antigen, it was demonstrated that the Fc-reacting antibodies, and the antiserum against human IgG, recognized an epitope on the pso p27 antigen. The data indicated that an antigenic determinant is shared by the p27 antigen(s) and human IgG, suggesting that p27 antigen(s) may act as antigen(s) eliciting the production of antibodies with rheumatoid factor activity in psoriatic patients.

Animals↗
PubMed1977

Characterization of tumour virus proteins. I. Radioimmunoassay of the P27 protein of avian viruses.

The major structural protein of avian oncornaviruses, a core component of about 27000 daltons, has been measured by radioimmunoassay. The purified protein was labelled with 125Iodine by chloramine-T method. The immune serum titer was defined as the highest serum dilution able to precipitate 50% of the labelled antigen present in the system. Standard competition curve was constructed in order to determine the equivalents of protein, in a system with limiting antibody concentration. In the experimental conditions used, 0.14 ng of AMV-P27 inhibited 50% of 125I-AMV-P27 (1.0 ng) precipitation. The 125I-AMV-P27 vs anti-AMV-P27 system was used to study the competition of normal cells, purified virus suspension, productive cells and supernatant fluids. Most of the chicken embryo fibroblasts showed expression of this viral component. The phenomena of cell transformation, the increase in total protein, and the expression of P27 were studied in rapid transformation of CEF by RSV-SRA.

Alpharetrovirus↗
PubMed1990

SIV, STLV-I and type D retrovirus antibodies in captive rhesus macaques and immunoblot reactivity to SIV p27 in human and rhesus monkey sera.

The prevalence of simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus type 1 (STLV-I), and type D retrovirus (SRV-D) antibodies was determined for 1229 rhesus monkeys (Macaca mulatta) from two research colonies. Serum samples were tested by using enzyme-linked immunosorbent assay (ELISA), immunoblot (IB), and radioimmunoprecipitation assay (RIPA). Seropositive results for the three retroviruses tested were 0 for SIV, 270 (22%) for STLV-I, and 103 (8.4%) for type D retrovirus. Of the rhesus monkey sera, 61 (5.0%) were reactive to SIV gag p27 only, when tested by IB, but were negative when further tested by RIPA. Virus isolation was attempted from cultured peripheral blood mononuclear cells of 35 monkeys whose sera contained only p27 reactivity and none were positive by reverse transcriptase and core antigen assays to detect SIV. No overt clinical signs of immunodeficiency disease or unexplained deaths were evident in either monkey colony. Additionally, 63 of 165 (38%) human sera from various groups (primate center workers, normal donors, health care workers) had weak to moderate IB reactivity only to SIV p27, but 31 of 31 sera tested were negative by RIPA. These sera remained reactive to SIV p27 following absorption with an uninfected cell lysate, after blocking IB strips with various blocking solutions and were reactive to different SIV antigen preparations while remaining negative to human immunodeficiency virus type 1 (HIV-1) by IB and negative to HIV-2 by ELISA. These data underscore the need to adopt criteria for a positive SIV serologic test requiring reactivity against more than one viral gene product. These results also illustrate a potential problem in the testing of human sera for antibodies against simian retroviruses and demonstrate the need for caution in the interpretation of immunoblot results.

Animals↗
PubMed1976

Presence of the p27 antigenicity and absence of the gp52 antigenicity and leukemia virus antigens in intracytoplasmic A particles (iAp) of mouse mammary tumour origin.

Using the Ouchterlony immunodiffusion method and indirect immunofluorescence tests on tissue slices the antigenic structure of iAp of mouse mammary tumour origin has further been investigated. Antisera against iAp, MTV-B particles, B particle polypeptide p27 and glycoprotein gp52, and leukemia C-type particles were used in these studies. The most prominent antigen of iAp in mammary tumours was found to be identical to the p27 antigen of B particles. This finding was not unexpected in view of recently published data by other authors showing the presence of p27 in iAp of leukemia cells and Leydig cell tumours. The p27 polypeptide is considered to be a group-specific antigen of mouse mammary tumour viruses associated with iAp of different tissue sources and inner structural components of mature B particles. On the other hand, the gp52 antigen and leukemia virus antigens were shown to be absent from iAp of mammary carcinomas. Therefore, the assumption is confirmed that the gp52 glycoprotein represents a group-specific antigen of B type viruses, presumably located at the virion surface. The failure to demonstrate leukemia virus antigens in iAp supports the suggestion that this kind of particles is not related to C type viruses.

Animals↗
PubMed1992

Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen.

We have previously shown that immunization with solid matrix-antigen-antibody (SMAA) complexes induces both vigorous humoral and cell-mediated immune responses and have suggested that this method of vaccination may be developed for use in humans, and potentially as a vaccine against AIDS. Here we demonstrate that a small oligopeptide can act as a tag for the construction of SMAA complexes using a tag-specific monoclonal antibody and tag-linked antigens. We show that a 14-amino acid oligopeptide, present in the phospho (P) and V proteins of simian virus 5 (SV5), retains its antigenicity when attached to the C terminus of three 'foreign' proteins [p27 and gp110 of simian immunodeficiency virus (SIV) and glutathione S-transferase] such that these proteins can be incorporated into SMAA complexes using a monoclonal antibody (MAb) that was originally raised against the native SV5 P and V proteins. Mice were immunized with SMAA complexes containing recombinant p27-TAG and MAbs have been isolated that recognized native SIV p27. The significance of these results in terms of the development of SMAA complexes as human vaccines is discussed.

Amino Acid Sequence↗
PubMed1992

HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in nef p27 and gag p25 proteins.

Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia virus recombinants. Proliferative responses of spleen cells were comparable against env gp160, nef p27, and gag p25 recombinant proteins. No specific activity was observed against gag p18 protein. Env, nef, and gag-specific T-cell lines were generated by repeated stimulation of immune spleen cells with recombinant HIV-1 proteins. They were CD4 positive, proliferative, and also cytotoxic against HIV-transfected target cells. Specificity of the T-cell response against nef and gag protein was analyzed with synthetic peptides. Peptides nef 15, nef 16, and gag AM-30 were, respectively, reactive in nef- and gag-specific proliferative and cytolytic assays. The three peptides described have a relatively conserved amino acid sequence among HIV isolates and appear broadly immunoreactive among species.

Amino Acid Sequence↗
PubMed1979

Family with three apparently balanced t(3;15) (p27;q22) translocation carriers. Association with deficits in language acquisition and mental retardation: a possible example of position effect in man.

A father, son, and daughter had a (3;15) (p27;q22) simple reciprocal translocation. No abnormality in the G-banding pattern was noted. The girl was most severely affected; she had an abnormal phenotype, noticeable delay in receptive and expressive language development, bilateral hearing impairment, and definite mental retardation. The boy had a moderate delay in receptive language skills, had moderate hearing impairment in one ear, and showed mild mental retardation. The father has low-set ears, some deficits in receptive language skills, is illiterate, and was found to be borderline mentally retarded. The mother and younger child do not have the translocation and are normal in terms of phenotype, intellect, and verbal skills. The accumulating evidence suggests that balanced translocations are associated with an increased frequency of intellectual deficit and congenital anomalies, and the cytogenetic mechanism may be that of position effect.

Adult↗
PubMed1979

11q aneuploidy: partial monosomy and trisomy in the children of a mother with a t(3;11)(p27;q23) translocation.

A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared with each other and with reported examples. Moreover, 11q break points are discussed.

Adult↗
PubMed1975

Localization of the major group-specific protein (p27) of avian tumor viruses by immunofluorescence in chicken cells and tissues.

An immunofluorescence technique was developed for the major group-specific (gs) p27 antigen of avian type C viruses. The localization of this antigen virus-infected in chick embryo fibroblasts was perinuclear, intracytoplasmic and at the cell surface in the majority of the cells, while it was at the cell surface only in some of the cells. No antigen was found in the nucleus. When chickens were experimentally infected with RAV-1 or a wild-strain avian leukosis virus (of subgroup A), the viral gs antigen was detected in lymphocytes of bursa of Fabricius and the spleen. Distinct specific staining was seen in the medulla of germinal centers in bursas of Fabricius and in the white pulp of the spleen where B lymphocytes are thought to be located. This is consistent with the possibility that B lymphocytes are the target cells in the infection of chickens with avian leukemia viruses.

Alpharetrovirus↗
PubMed1992

Effect of myristoylation on p27 nef subcellular distribution and suppression of HIV-LTR transcription.

The effect of myristoylation on p27nef subcellular distribution and suppression of HIV-1 transcription was examined by transfecting COS-7 cells with plasmids expressing either myristoylated (pSVnef) or nonmyristolyated p27nef (pSVnefala2). Similar levels of myristoylated and nonmyristoylated p27nef were expressed with only the product of the pSVnef plasmid being myristoylated. Immuno-histochemical microscopy and radioimmunoprecipitation revealed myristolyated p27nef only in the membrane fraction while nonmyristolyated p27nef was found distributed between the nucleus and the cytosol fractions. The effect of myristoylation on p27nef suppression of HIV LTR controlled transcription was examined in transient transfected COS cells and in CEM human T-cell clones consituitively expressing either myristolyated or nonmyristolyated p27nef by cotransfecting with a chloramphenicol acetyltransferase (CAT) plasmid under control of the HIV-1 LTR. In both systems, myristoylated p27nef exhibited a 13- to 18-fold inhibition of basal CAT activity while the nonmyristolyated mutant and the same plasmid carrying the nef gene in a reverse orientation inhibited CAT activity one- to two-fold. These results confirm the cytoplasmic membrane localization of p27nef and establish that its subcellular targeting is dependent on covalently attached myristate. The data also provide further evidence that p27nef acts as a transcriptional suppressor and establishes for the first time that myristolyation is required for the full manifestation of this effect.

Cell Line↗
PubMed1978

Polyproteins related to the major core protein of mouse mammary tumor virus.

The mouse mammary tumor virus (MuMTV) contains several low-molecular-weight proteins which, together with the genomic RNA, constitute the core structure of the virion. The most abundant protein in the core is the 27,000-dalton protein (p27), and, by analogy to the type C viruses, this protein probably forms the core shell. In mouse mammary tumor cell lines (GR and Mm5MT) producing MuMTV the major p57 antigenic specificity resides in a large protein, which migrates in polyacrylamide gels as a doublet of 77,000 and 75,000 daltons (p 77/75). A series of lower-molecular-weight proteins, p61, p48, p38, and p34, is also present in small amounts and is probably derived by proteolytic cleavage of the p 77/75. These proteins have been identified by immunoprecipitation with monospecific antiserum, and their sequence relatedness to p27 has been determined by an analysis of the peptides after trypsin digestion. After a 15-min pulse with [35S]-methionine, all of the p27-related proteins in these cell lines were labelled and, during a subsequent chase, progressively disappeared. The p27 was labeled poorly during the pulse, but the amount of label in this protein increased during the chase. A quantitation of these experiments suggested that the majority of the p27-related proteins were quite rapidly turned over in these cell lines. Hence, if p27 is derived by a progressive proteolytic cleavage mechanism, then the process is inefficient in the GR cells and only moderately efficient in the Mm5MT cells. When MuMTV was isolated from the culture medium of these cells harvested at 5-min intervals, the major p27-related protein was p34. The p27 accounted for only 29% of the anti-p27 serum immunoprecipitable proteins compared to 95% in virus isolated from an 18-h harvest. Incubation of the rapid-harvest virus at 37 degrees C for 2 h resulted in some conversion of p34 to p27. These results suggest that some of the p27 in MuMTV is formed in the virions by proteolytic cleavage of p34.

Animals↗
PubMed1990

Immunogenicity of the human immunodeficiency virus (HIV) recombinant nef gene product. Mapping of T-cell and B-cell epitopes in immunized chimpanzees.

The nonstructural nef gene product of human immunodeficiency virus (HIV), p27, is a regulatory "early phase" protein produced by HIV-infected cells. As a possible negative regulator of transcription, it has been suggested that p27 may be involved in the control of HIV proviral latency. Immune reactivity to p27 may result in early destruction of HIV-replicating cells before viral assembly or of latently infected cells. It appeared, thus, of interest to investigate the immunogenicity of the molecule in chimpanzees immunized against HIV antigens. Two of the six chimpanzees that were injected with soluble recombinant p27 in association with other HIV proteins, displayed significant and sustained T-helper lymphocyte proliferative responses to p27 and to the other antigens. Using a set of synthetic peptides spanning the entire p27 sequence, two T-cell epitopes could be located: one within the last 20 amino-acids of the C terminus of the molecule, the other around the region of residues 118-122. Sera from the same animals also reacted to p27 in a radioimmunoassay as well as to some of the peptides in enzyme-linked immunosorbent assay. Sequential B-cell epitopes could thus be determined as being located in the regions of amino acids: 17-35, 52-66, and 185-205. The results obtained with peptides spanning the region between amino acid residues 65 and 172 indicate that at least two additional B-cell epitopes were present in the region comprised between amino acid 65 and 146. Interestingly, the extreme C terminus of the molecule encompasses both immunodominant T- and B-cell epitopes. Taken together, these observations should prove useful for the rational design of a HIV vaccine.

Amino Acid Sequence↗
PubMed2026

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with ≥pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities↗
PubMed1976

Antigenic analysis of the major structural protein of the Mason-Pfizer monkey virus.

The major internal protein, p27 (m.w. 27,000 daltons) of the Mason-Pfizer monkey virus (MPMV) was purified by gel filtration and ion-exchange chromatography and then used to develop a radioimmunoassay (RIA). This RIA was specific for MPMV because no immunologic cross-reactivity was observed between p27 of MPMV and 13 different RNA tumor viruses of mammalian and avian origin. However, the p27 of MPMV grown in three different primate cells exhibited identical antigenic cross-reactivity. In addition, significant levels of p27 were found only in MPMV-infected cells. These results indicate that synthesis of p27 is induced after virus infection and that p27 represents a viral-coded protein.

Animals↗
PubMed1977

Structural protein markers in the avian oncoviruses.

The proteins of purified avian oncoviruses were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and isoelectric focusing. Certain members of the avian leukosis-sarcoma viruses (ALSV) had group-specific antigens with altered electrophoretic properties. (i) The p27 protein of Rous-associated virus 0 (RAV-0) had a lower electrophoretic mobility in SDS gels and a lower isoelectric point than the p27 of other ALSV. (ii) The p19 proteins of RAV-1, RAV-2, and the Bryan high-titer strain of Rous sarcoma virus had higher mobilities in SDS gels than did the corresponding protein of other viruses. This altered electrophoretic mobility was correlated with specific differences in the tryptic peptides of radioiodinated p19s. (iii) The p15 protein of RAV-7 had a lower mobility in SDS gels than did the p15 of other ALSV. These markers were used in a study of the structural proteins of subgroup E RAV-60 produced after infection of chicken embryo cells by exogenous ALSV. Although exogenous group-specific protein markers could often be identified in the subgroup E isolates, one RAV-60 had a p27 that comigrated with the p27 of RAV-0. The p19s of two other RAV-60 isolates had electrophoretic properties that were different than those of p19s from either RAV-0 or the exogenous viruses. These results support the hypothesis that RAV-60 is generated by recombination between endogenous and exogenous oncoviruses and indicate that at least the p27 encoded by RAV-0 is closely related to a protein specified by endogenous viral information in chicken cells.

Autoradiography↗
PubMed1992

Purification of immature cores of mouse mammary tumor virus and immunolocalization of protein domains.

The immature capsids of the mouse mammary tumor virus (MMTV), known as intracytoplasmic A particles, have been isolated from murine L1210 leukemia cells. The diameter of the isolated particles was 80 nm as determined by negative staining. Two polypeptides of 77 and 110 kDa were found to be their major polypeptide components, in agreement with the expected sizes of the Gag and Gag-Pro precursor polypeptides of the mature MMTV proteins. Both polypeptides were recognized by antibodies directed toward the matrix (p10) and capsid (p27) proteins of MMTV. Immunogold labeling of p10 on isolated A particles, visualized by negative staining, showed that this protein is located at the surface of the immature capsids, whereas p27 can be detected only in broken or disrupted particles, suggesting that it has an internal location. These observations were confirmed by immunolabeling of both proteins on thin sections of A particle-producing cells. In addition, the viral protease had a more internal position than p27. Since the sequential order of the viral proteins in the Gag precursor is p10-pp21-p27-p14 and that in Gag-Pro is p10-pp21-p27-p30-protease, our results demonstrate the radial organization of the polypeptide precursors forming the intracytoplasmic A particles.

Amino Acid Sequence↗