ets-2 regulates cdc2 kinase activity in mammalian cells: coordinated expression of cdc2 and cyclin A.
ets-2 is a member of a family of transcription factors implicated in the regulation of gene expression during cell proliferation, cell differentiation, and development. We report that the ets-2 protein transactivates the promoter of the cdc2 gene which encodes a 34-kDa serine-threonine kinase required for mitotic initiation in mammalian cells. Transactivation occurs via specific interaction with multiple ets binding sites in the 5' flanking region of the gene. In BALB/c3T3 rodent fibroblasts constitutively expressing ets-2 and cultured in either 10 or 0.5% serum, cdc2 expression and its associated histone H1 kinase activity are increased, compared to control cells. Such increased activity correlates with elevated levels of cyclin A but not cyclin B1. Furthermore, ets-2-transfected, but not parental, BALB/c3T3 cells, grow under low serum conditions, albeit at a reduced rate. These data demonstrate that ets-2 plays a direct role in the regulation of cdc2 expression and raise the possibility that ets-2 participates in the coordinated regulation of cdc2 cyclin A expression which is essential for the modulation of cdc2-regulated processes.
Wen
S C
SC
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Ku
D H
DH
De Luca
A
A
Claudio
P P
PP
Giordano
A
A
Calabretta
B
B
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000096:biosynthesis*; D002455:Cell Division / Q000502:physiology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D016213:Cyclins; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D016203:CDC2 Protein Kinase