PMID- 10564259 OWN - NLM STAT- MEDLINE DCOM- 19991209 LR - 20181113 IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 10 IP - 11 DP - 1999 Nov TI - Mechanisms of G2 arrest in response to overexpression of p53. PG - 3607-22 AB - Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was suppressed in response to the induction of p53. Suppression requires the regions -287 to -123 of the cyclin B1 promoter and -104 to -74 of the cdc2 promoter. p53 did not affect the inhibitory phosphorylations of CDC2 at threonine 14 or tyrosine 15 or the activity of the cyclin-dependent kinase that activates CDC2 by phosphorylating it at threonine 161. Overexpression of p53 may also interfere with the accumulation of CDC2/cyclin B1 in the nucleus, required for cells to enter mitosis. Constitutive expression of cyclin B1, alone or in combination with the constitutively active CDC2 protein T14A Y15F, did not reverse p53-dependent G2 arrest. However, targeting cyclin B1 to the nucleus in cells also expressing CDC2 T14A Y15F did overcome this arrest. It is likely that several distinct pathways contribute to p53-dependent G2 arrest. FAU - Taylor, W R AU - Taylor WR AD - Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. FAU - DePrimo, S E AU - DePrimo SE FAU - Agarwal, A AU - Agarwal A FAU - Agarwal, M L AU - Agarwal ML FAU - Schonthal, A H AU - Schonthal AH FAU - Katula, K S AU - Katula KS FAU - Stark, G R AU - Stark GR LA - eng GR - R01 GM049345/GM/NIGMS NIH HHS/United States GR - GM-49345/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (CCNB1 protein, human) RN - 0 (Cyclin B) RN - 0 (Cyclin B1) RN - 0 (RNA, Messenger) RN - 0 (Tumor Suppressor Protein p53) RN - 500-44-7 (Mimosine) RN - 9007-49-2 (DNA) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) RN - EC 2.7.11.22 (CDC2 Protein Kinase) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) RN - EC 2.7.11.22 (cyclin-dependent kinase-activating kinase) SB - IM MH - Apoptosis/*genetics MH - CDC2 Protein Kinase/genetics MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Nucleus/genetics MH - Cyclin B/genetics MH - Cyclin B1 MH - *Cyclin-Dependent Kinases MH - DNA/biosynthesis MH - Flow Cytometry MH - G2 Phase/*genetics MH - Gene Expression Regulation MH - Humans MH - Microscopy, Video MH - Mimosine/pharmacology MH - Mitosis MH - Phosphorylation MH - Promoter Regions, Genetic MH - Protein-Serine-Threonine Kinases/metabolism MH - RNA, Messenger/metabolism MH - Tumor Suppressor Protein p53/*metabolism PMC - PMC25646 EDAT- 1999/11/17 00:00 MHDA- 1999/11/17 00:01 CRDT- 1999/11/17 00:00 PHST- 1999/11/17 00:00 [pubmed] PHST- 1999/11/17 00:01 [medline] PHST- 1999/11/17 00:00 [entrez] AID - 10.1091/mbc.10.11.3607 [doi] PST - ppublish SO - Mol Biol Cell. 1999 Nov;10(11):3607-22. doi: 10.1091/mbc.10.11.3607.