E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. Genes Dev 1995 Dec 01;9(23):2873-87
Date
12/01/1995Pubmed ID
7498785DOI
10.1101/gad.9.23.2873Scopus ID
2-s2.0-0028826881 (requires institutional sign-in at Scopus site) 203 CitationsAbstract
Numerous experiments have defined a critical role for the G1 cyclins and associated kinases in allowing a normal progression of cells from a quiescent state, through G1, and into S phase. We now demonstrate that G1 cyclin-dependent kinase activity is critical for the accumulation of E2F activity late in G1. Moreover, E2F-1 overexpression can overcome a G1 arrest caused by the inhibition of G1 cyclin-dependent kinase activity, consistent with E2F activation being an important consequence of the action of G1 cyclins. E2F-1 also overcomes a G1 block caused by gamma irradiation and leads to an apparent complete replication of the cellular genome and entry into mitosis. This E2F-1-mediated induction of S phase and mitosis is not accompanied by the rise in either cyclin D-associated kinase activity or cdk2 activity that is normally observed during the G1 phase of the cell cycle. We conclude that one key function for G1 cyclin-dependent kinase activity is the activation of E2F-1, that the accumulation of E2F activity may be sufficient to allow initiation and completion of S phase, but that additional events, including G1 cyclin kinase activity, are likely necessary for a normal proliferative event.
Author List
DeGregori J, Leone G, Ohtani K, Miron A, Nevins JRAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blotting, WesternCDC2-CDC28 Kinases
Carrier Proteins
Cell Cycle Proteins
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases
DNA
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
G1 Phase
G2 Phase
Gamma Rays
Gene Expression Regulation
Microtubule-Associated Proteins
Mitosis
Plasmids
Promoter Regions, Genetic
Retinoblastoma Protein
Retinoblastoma-Binding Protein 1
S Phase
Transcription Factors
Tumor Suppressor Proteins
