title: Cyclin-dependent kinase 5 regulates E2F transcription factor through phosphorylation of Rb protein in neurons.
abstract: 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.
authors.affiliation: Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Futatsugi
authors.forename: Elias
authors.initials: E
authors.lastname: Utreras
authors.forename: Parvathi
authors.initials: P
authors.lastname: Rudrabhatla
authors.forename: Howard
authors.initials: H
authors.lastname: Jaffe
authors.forename: Harish C
authors.initials: HC
authors.lastname: Pant
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D050684:E2F Transcription Factors; D009419:Nerve Tissue Proteins; D010748:Phosphopeptides; D016160:Retinoblastoma Protein; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5