Document Detail


Involvement of pRB-related p107 protein in the inhibition of S phase progression in response to genotoxic stress.
MedLine Citation:
PMID:  11278582     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
pRB family pocket proteins consisting of pRB, p107, and p130 are thought to act as a set of growth regulators that inhibit the cell cycle transition from G1 to S phases by virtue of their interaction with E2F transcription factors. When cells are committed to progressing through the cell cycle at the late G1 restriction point, they are hyperphosphorylated by G1 cyclin-cyclin-dependent kinase and are functionally inactivated. Consistent with such a G1 regulatory role, pRB and p130 are abundantly expressed in quiescent cells. In contrast, p107 is present at low levels in the hypophosphorylated form in quiescent cells. As cells progress toward late G1 to S phases, the levels of p107 increase, and the majority become hyperphosphorylated, suggesting a possible role of p107 in post-G1 cell cycle regulation. In this study, we have demonstrated that a nonphosphorylatable and thus constitutively active p107 has the potential to inhibit S phase progression. The levels of the phosphorylation-resistant p107 required for the S phase inhibition are significantly less than those of endogenous p107. We further show herein that the exposure of cells to the DNA-damaging agent, cisplatin, provokes S phase arrest, which is concomitantly associated with the accumulation of hypophosphorylated p107. Furthermore, the S phase inhibitory response to cisplatin is augmented by the ectopic expression of wild type p107, although it is diminished by the adenovirus E1A oncoprotein, which counteracts the pocket protein functions. Because p107 is a major pRB family protein expressed in S phase cells, our results indicate that p107 participates in an inhibition of cell cycle progression in response to DNA damage in S phase cells.
Authors:
T Kondo; H Higashi; H Nishizawa; S Ishikawa; S Ashizawa; M Yamada; Z Makita; T Koike; M Hatakeyama
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-02-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-23     Completed Date:  2001-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17559-67     Citation Subset:  IM    
Affiliation:
Division of Molecular Oncology, Institute for Genetic Medicine, Department of Medicine II, School of Medicine, Hokkaido University, Kita-ku, Sapporo 060, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
COS Cells
Cell Cycle / drug effects,  physiology*
Cell Line
Cercopithecus aethiops
Culture Media, Conditioned
Humans
Hydroxyurea / pharmacology
Interleukin-3 / pharmacology
Lymphocytes / cytology,  drug effects
Mice
Mutagenesis, Site-Directed
Nocodazole / pharmacology
Nuclear Proteins / chemistry,  genetics,  metabolism*
Phosphorylation
Recombinant Proteins / chemistry,  metabolism
Retinoblastoma Protein / metabolism*
Retinoblastoma-Like Protein p107
S Phase
Sequence Deletion
Serine
Threonine
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Interleukin-3; 0/Nuclear Proteins; 0/RBL1 protein, human; 0/Rbl1 protein, mouse; 0/Recombinant Proteins; 0/Retinoblastoma Protein; 0/Retinoblastoma-Like Protein p107; 127-07-1/Hydroxyurea; 31430-18-9/Nocodazole; 56-45-1/Serine; 72-19-5/Threonine

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