Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation

Article Article scientifique Article Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation eng 2011 author Bonnefont Jérôme 634357 author Laforge T author Plastre Olivier 641822 author Beck Brian Victor 84919 author Sorce Silvia 603660 author Dehay C author Krause Karl-Heinz 23022 293-303 10.1038/cdd.2010.102 20725088 1350-9047 Ret finger protein-like 1 (RFPL1) is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development. However, its cellular activity remains elusive. In this article, we report that Pax6-elicited expression of the human (h)RFPL1 gene in HeLa cells can be enhanced by in vivo p53 binding to its promoter and therefore investigated the hypothesis that hRFPL1 regulates cell-cycle progression. Upon expression in these cells, hRFPL1 decreased cell number through a kinase-dependent mechanism as PKC activates and Cdc2 inhibits hRFPL1 activity. hRFPL1 antiproliferative activity led to an increased cell population in G(2)/M phase and specific cyclin B1 and Cdc2 downregulations, which were precluded by a proteasome inhibitor. Specifically, cytoplasm-localized hRFPL1 prevented cyclin B1 and Cdc2 accumulation during interphase. Consequently, cells showed a delayed entry into mitosis and cell-cycle lengthening resulting from a threefold increase in G(2) phase duration. Given previous reports that RFPL1 is expressed during cell differentiation, its impact on cell-cycle lengthening therefore provides novel insights into primate-specific development. Animals Carrier Proteins/genetics/metabolism/physiology Cell Division Cyclin B/metabolism Cyclin B1/metabolism Eye Proteins/metabolism G2 Phase HeLa Cells Homeodomain Proteins/metabolism Humans Interphase Mitosis Paired Box Transcription Factors/metabolism Primates/metabolism Promoter Regions, Genetic Protein Binding Protein Kinase C/metabolism Repressor Proteins/metabolism Tumor Suppressor Protein p53/metabolism Dewey 616.07 137 Département de pathologie et immunologie 21F false 38 Radicaux libres et cellules souches embryonnaires 60 Cell death and differentiation 18 2 8e75c953-ae5b-4fe8-9958-f2073e46d857 Article (Published version) Restricted 2011 Feb Krause Primate-specific RFPL1.pdf 457681 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation	Cell death and differentiation			2011	648	0

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Beck, Brian Victor