Inactivation of pRB-Related Proteins p130 and p107 Mediated by the J Domain of Simian Virus 40 Large T Antigen
| Autor: | Kathryn S. Campbell, Hilde Stubdal, Colleen Schweitzer, Juan Zalvide, James A. DeCaprio, Thomas M. Roberts |
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| Rok vydání: | 1997 |
| Předmět: |
Proteasome Endopeptidase Complex
Antigens Polyomavirus Transforming Molecular Sequence Data Mutant Retinoblastoma-Like Protein p107 Biology DNAJ Protein Retinoblastoma Protein Mice Multienzyme Complexes Tumor Cells Cultured Animals Humans Amino Acid Sequence Phosphorylation Nuclear protein Molecular Biology Peptide sequence Heat-Shock Proteins Binding Sites Retinoblastoma-Like Protein p130 Retinoblastoma protein Nuclear Proteins Proteins Cell Biology HSP40 Heat-Shock Proteins Phosphoproteins Molecular biology Growth Inhibitors Cysteine Endopeptidases embryonic structures biology.protein biological phenomena cell phenomena and immunity Sequence Alignment Research Article Myc-tag |
| Zdroj: | Molecular and Cellular Biology. 17:4979-4990 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.17.9.4979 |
| Popis: | Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J-domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homology region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg. |
| Databáze: | OpenAIRE |
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