Identification of murine cdk10: association with Ets2 transcription factor and effects on the cell cycle
Luigi Bagella1, Cristina Giacinti, Cristiano Simone
1Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA. bagella@temple.edu
Abstract:
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.
Insights
Murine cdk10, a cell cycle regulator, binds Ets2 transcription factors but does not impact cell proliferation or the G2/M transition, unlike its human counterpart which has multiple isoforms.
Area of Science:
- Molecular Biology
- Cell Cycle Regulation
- Protein Kinases
Background:
- Cyclin-dependent kinases (cdks) are crucial regulators of the eukaryotic cell cycle, activated by cyclins.
- Human cdk10 exhibits two isoforms with distinct functions, including roles in cell cycle transition and transcription factor interaction.
- Cdk10 contains conserved kinase motifs like PSTAIRE-like PISSLRE.
Purpose of the Study:
- To clone and functionally characterize the murine homologue of cdk10.
- To investigate the role of murine cdk10 in cell cycle progression and transcription factor binding.
Main Methods:
- Cloning of murine cdk10 cDNA.
- In vitro binding assays with Ets2 transcription factors.
- Analysis of cell proliferation rates and G2/M transition in cell lines expressing murine cdk10.
Main Results:
- A single murine cdk10 cDNA encoding a 360-amino acid protein was identified, showing high homology to human cdk10.
- Murine cdk10 demonstrated in vitro binding to Ets2 transcription factors.
- Murine cdk10 did not exhibit direct involvement in the G2/M transition or affect cell proliferation rates.
Conclusions:
- Murine cdk10 interacts with Ets2 transcription factors but appears to have a different functional role compared to human isoforms.
- The unique murine cdk10 does not directly regulate the cell cycle at the G2/M transition or influence cell proliferation.
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