Differential regulation of the retinoblastoma family of proteins during cell proliferation and differentiation
Open Access
- 1 August 1998
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 333 (3), 645-654
- https://doi.org/10.1042/bj3330645
Abstract
In the present study we have analysed the regulation of pocket protein expression and post-transcriptional modifications on cell proliferation and differentiation, both in vivo and in vitro. There are marked changes in pocket protein levels during these transitions, the most striking differences being observed between p130 and p107. The mechanisms responsible for regulating pocket protein levels seem to be dependent on both cell type and pocket protein, in addition to their dependence on the cell growth status. Changes in retinoblastoma protein and p107 levels are independent of their state of phosphorylation. However, whereas p130 phosphorylation to forms characteristic of quiescent/differentiated cells results in the accumulation of p130 protein, phosphorylation of p130 to one or more forms characteristic of cycling cells is accompanied by down-regulation of its protein levels. We also show here that the phosphorylation status and protein levels of p130 and p107 are regulated in vivo as in cultured cells. In vivo, changes in p130 forms are correlated with changes in E2F complexes. Moreover, the modulation of p130 and p107 status during cell differentiation in vitro is consistent with the patterns of protein expression and phosphorylation status found in mouse tissues. Thus in addition to the direct disruption of pocket protein/E2F complexes induced by cyclin/cyclin-dependent kinase, the results we report here indicate that the differential modulation of pocket protein levels constitutes a major mechanism that regulates the pool of each pocket protein that is accessible to E2F and/or other transcription factors.Keywords
This publication has 40 references indexed in Scilit:
- pRB, p107 and p130 as transcriptional regulators: Role in cell growth and differentiationPublished by Springer Science and Business Media LLC ,1997
- Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes.Molecular and Cellular Biology, 1993
- Cell cycle-specific association of E2F with the p130 E1A-binding protein.Genes & Development, 1993
- v-myb blocks granulocyte colony-stimulating factor-induced myeloid cell differentiation but not proliferation.Molecular and Cellular Biology, 1993
- Smooth muscle cell outgrowth from human atherosclerotic plaque: Implications for the assessment of lesion biologyJournal of the American College of Cardiology, 1992
- A Simplified Method for the Preparation of Transcriptionally Active Liver Nuclear ExtractsDNA and Cell Biology, 1990
- Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutantCell, 1990
- Rapid detection of octamer binding proteins with ‘mini extracts’, prepared from a small number of cellsNucleic Acids Research, 1989
- Cytokine-dependent granulocytic differentiation. Regulation of proliferative and differentiative responses in a murine progenitor cell line.The Journal of Immunology, 1987
- THE KINETICS OF CELLULAR PROLIFERATION IN REGENERATING LIVERThe Journal of cell biology, 1968