Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation
| Autor: | Silvia Sorce, Brian Victor Beck, Jérôme Bonnefont, Karl-Heinz Krause, Colette Dehay, Olivier Plastre, Térèse Laforge |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
PAX6 Transcription Factor
Cyclin D Cellular differentiation Cyclin A Cyclin B Cyclin B/metabolism ddc:616.07 0302 clinical medicine Cyclin B1/metabolism Paired Box Transcription Factors Cyclin B1 Promoter Regions Genetic Protein Kinase C 0303 health sciences biology Cyclin-Dependent Kinases 030220 oncology & carcinogenesis Cell Division Protein Binding Primates G2 Phase Paired Box Transcription Factors/metabolism Eye Proteins/metabolism Mitosis Protein Kinase C/metabolism 03 medical and health sciences Cyclin-dependent kinase CDC2 Protein Kinase Animals Homeodomain Proteins/metabolism Humans Eye Proteins Molecular Biology Interphase Tumor Suppressor Protein p53/metabolism 030304 developmental biology Homeodomain Proteins Cyclin-dependent kinase 1 Original Paper Repressor Proteins/metabolism Primates/metabolism Cell Biology Repressor Proteins biology.protein Cancer research Tumor Suppressor Protein p53 Carrier Proteins/genetics/metabolism/physiology Carrier Proteins Cyclin A2 HeLa Cells |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, Vol. 18, No 2 (2011) pp. 293-303 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2010.102 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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