Regulation of the transcription factor FOXM1c by Cyclin E/CDK2.
The FOXM1 forkhead proteins, originally identified as M-phase phosphoproteins, are proliferation-associated transcriptional regulators involved in cell cycle progression, genetic stability and tumorigenesis. Here we demonstrate that Cyclin-dependent kinases regulate the transcriptional activity of FOXM1c. This is independent of an N-terminal negative regulatory domain and of the forkhead DNA binding domain. Instead we mapped the responsive sites in the transactivation domain. A combination of three phosphorylation sites mediates the Cyclin E and Cyclin A/CDK2 effects. Our findings provide evidence for a novel Cyclin E/CDK2 substrate that functions in cell cycle control.
Lüscher-Firzlaff
Juliane M
JM
Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Universitätsklinikum der RWTH, Pauwelsstrasse 30, 52057 Aachen, Germany.
Lilischkis
Richard
R
Lüscher
Bernhard
B
D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D019925:Cyclin A; D019927:Cyclin E / Q000235:genetics / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000502:physiology*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics
D019925:Cyclin A; D019927:Cyclin E; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D051357:Cyclin-Dependent Kinase 2