p21 Disrupts the interaction between cdk2 and the E2F-p130 complex.
In nonproliferating or growth-arrested cells, the transcription factor E2F remains bound to the retinoblastoma-related protein p130. Accumulation of this E2F-p130 complex correlates with an arrest of the cell cycle progression. Progression through G1 phase is associated with a cyclin-dependent binding of the cyclin-dependent kinase cdk2 to the E2F-p130 complex. By fractionating mouse L-cell extracts, we have obtained a partially purified preparation of the E2F-p130 complex that also contains cdk2. Incubation of this complex with recombinant p21 results in a disruption of the interaction between cdk2 and the E2F-p130 complex in extracts of a cell line that expresses a temperature-sensitive mutant of p53. Incubation at the permissive temperature (32 degrees C) results in an induction of p21 synthesis. An increase in the level of p21 in these cells correlates with a loss of cdk2 from the cdk2-containing E2F-p130 complex. We also show that the expression of a reporter gene containing E2F sites in the promoter region is reduced by the coexpression of p21. Since p21 is believed to be a mediator of p53, we speculated that the p21-mediated disruption of the cdk2-containing E2F-p130 complex plays a role in the growth suppression function of p53.
Shiyanov
P
P
Department of Biochemistry, University of Illinois at Chicago, Illinois 60612, USA.
Bagchi
S
S
Adami
G
G
Kokontis
J
J
Hay
N
N
Arroyo
M
M
Morozov
A
A
Raychaudhuri
P
P
D000818:Animals; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase; D005786:Gene Expression Regulation; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D010750:Phosphoproteins; D011506:Proteins; C493838:Rbl2 protein, mouse; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases