PMID- 22456337 OWN - NLM STAT- MEDLINE DCOM- 20120914 LR - 20211021 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 11 IP - 8 DP - 2012 Apr 15 TI - Cyclin-dependent kinase 5 regulates E2F transcription factor through phosphorylation of Rb protein in neurons. PG - 1603-10 LID - 10.4161/cc.20009 [doi] AB - Recent studies have shown the involvement of cyclin-dependent kinase 5 (Cdk5) in cell cycle regulation in postmitotic neurons. In this study, we demonstrate that Cdk5 and its co-activator p35 were detected in the nuclear fraction in neurons and Cdk5/p35 phosphorylated retinoblastoma (Rb) protein, a key protein controlling cell cycle re-entry. Cdk5/p35 phosphorylates Rb at the sites similar to those phosphorylated by Cdk4 and Cdk2. Furthermore, increased Cdk5 activity elevates activity of E2F transcription factor, which can trigger cell cycle re-entry, leading to neuronal cell death. A normal Cdk5 activity in neurons did not induce E2F activation, suggesting that Cdk5 does not induce cell cycle re-entry under normal conditions. Taken together, these results indicate that Cdk5 can regulate cell cycle by its ability to phosphorylate Rb. Most importantly, increased Cdk5 activity induces cell cycle re-entry, which is especially detrimental for survival of postmitotic neurons. FAU - Futatsugi, Akira AU - Futatsugi A AD - Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. FAU - Utreras, Elias AU - Utreras E FAU - Rudrabhatla, Parvathi AU - Rudrabhatla P FAU - Jaffe, Howard AU - Jaffe H FAU - Pant, Harish C AU - Pant HC FAU - Kulkarni, Ashok B AU - Kulkarni AB LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20120415 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (E2F Transcription Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Phosphopeptides) RN - 0 (Retinoblastoma Protein) RN - 0 (neuronal Cdk5 activator (p25-p35)) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) SB - IM CIN - Cell Cycle. 2012 Jun 1;11(11):2049. PMID: 22622087 MH - Amino Acid Sequence MH - Animals MH - Cyclin-Dependent Kinase 5/deficiency/genetics/*metabolism MH - E2F Transcription Factors/*metabolism MH - Mass Spectrometry MH - Mice MH - Molecular Sequence Data MH - Nerve Tissue Proteins/deficiency/genetics/metabolism MH - Neurons/*metabolism MH - Phosphopeptides/analysis MH - Phosphorylation MH - Retinoblastoma Protein/*metabolism PMC - PMC3341229 EDAT- 2012/03/30 06:00 MHDA- 2012/09/15 06:00 PMCR- 2013/04/15 CRDT- 2012/03/30 06:00 PHST- 2012/03/30 06:00 [entrez] PHST- 2012/03/30 06:00 [pubmed] PHST- 2012/09/15 06:00 [medline] PHST- 2013/04/15 00:00 [pmc-release] AID - 20009 [pii] AID - 2011CC3869R [pii] AID - 10.4161/cc.20009 [doi] PST - ppublish SO - Cell Cycle. 2012 Apr 15;11(8):1603-10. doi: 10.4161/cc.20009. Epub 2012 Apr 15.