Identification of murine cdk10: association with Ets2 transcription factor and effects on the cell cycle.
Cyclin-dependent kinases (cdks) are the catalytic subunits of a large family of serine/threonine protein kinases whose best-characterized members are key regulators of eukaryotic cell cycle progression. They are activated by binding to regulatory subunits generally termed as cyclins. Cdk10 is a cdc2-related kinase that contains the canonical regulatory Tyr and Thr residues present in all protein kinases and a PSTAIRE-like motif named PISSLRE. Although little is known about this protein, human cdk10 has been shown to encode two different isoforms, each having a distinct function. They differ at both the carboxy- and amino-terminals, although most of the amino acid sequence is predicted to be identical for the two isoforms. A role at the G2/M transition has been suggested for an isoform of cdk10, while the alternative splicing form interacts with the N-terminus of the Ets2 transcription factor. Here we report the cloning and the functional characterization of a cDNA encoding the murine homologue of cdk10. Unlike its human counterpart, only one murine cdk10 protein has been identified, and this unique murine cdk10 cDNA encodes a putative protein of 360 amino acids. Comparison of the amino acid sequences of murine and human cdk10 shows high homology. Murine cdk10 binds Ets2 transcription factors in vitro, does not show a direct involvement in the G2/M transition and, therefore, does not affect the proliferation rate of the cell lines analyzed.
Bagella
Luigi
L
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA. bagella@temple.edu
Giacinti
Cristina
C
Simone
Cristiano
C
Giordano
Antonio
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014018:Tissue Distribution
C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; C501014:Cdk10 protein, mouse; D018844:Cyclin-Dependent Kinases