HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 20, 17559-17567, May 18, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/20/17559    most recent M009911200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kondo, T. Articles by Hatakeyama, M. Search for Related Content PubMed PubMed Citation Articles by Kondo, T. Articles by Hatakeyama, M. Social Bookmarking                      What's this?

Involvement of pRB-related p107 Protein in the Inhibition of S Phase Progression in Response to Genotoxic Stress^*

Takuma Kondo^§, Hideaki Higashi^§, Hiroko Nishizawa^§, Susumu Ishikawa^§, Satoshi Ashizawa^§, Masafumi Yamada^§, Zenji Makita^¶, Takao Koike^¶, and Masanori Hatakeyama^§

From the  Division of Molecular Oncology, Institute for Genetic Medicine, ^¶ Department of Medicine II, School of Medicine, Hokkaido University, Kita-ku, Sapporo 060, and the ^§ Department of Viral Oncology, Cancer Institute, Japanese Foundation for Cancer Research, Toshima-ku, Tokyo 170, Japan

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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				T. E. Lyons, M. Salih, and B. S. Tuana Activating E2Fs mediate transcriptional regulation of human E2F6 repressor Am J Physiol Cell Physiol, January 1, 2006; 290(1): C189 - C199. [Abstract] [Full Text] [PDF]

				J. White, E. Stead, R. Faast, S. Conn, P. Cartwright, and S. Dalton Developmental Activation of the Rb-E2F Pathway and Establishment of Cell Cycle-regulated Cyclin-dependent Kinase Activity during Embryonic Stem Cell Differentiation Mol. Biol. Cell, April 1, 2005; 16(4): 2018 - 2027. [Abstract] [Full Text] [PDF]

				T. Takebayashi, H. Higashi, H. Sudo, H. Ozawa, E. Suzuki, O. Shirado, H. Katoh, and M. Hatakeyama NF-kappa B-dependent Induction of Cyclin D1 by Retinoblastoma Protein (pRB) Family Proteins and Tumor-derived pRB Mutants J. Biol. Chem., April 18, 2003; 278(17): 14897 - 14905. [Abstract] [Full Text] [PDF]

				E. Laplantine, F. Rossi, M. Sahni, C. Basilico, and D. Cobrinik FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest J. Cell Biol., August 19, 2002; 158(4): 741 - 750. [Abstract] [Full Text] [PDF]

				S. Agrawal, M. L. Agarwal, M. Chatterjee-Kishore, G. R. Stark, and G. M. Chisolm Stat1-Dependent, p53-Independent Expression of p21waf1 Modulates Oxysterol-Induced Apoptosis Mol. Cell. Biol., April 1, 2002; 22(7): 1981 - 1992. [Abstract] [Full Text] [PDF]