Created 19/01/2024
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CDK10 has long remained one of the most mysterious CDKs (cyclin-dependent kinases), in the absence of a known activating cyclin. We identified an activating cyclin (CycM, recently renamed Q), revealed the kinase activity of CDK10/CycQ, unveiled its role in the control of ETS2 stability and in ciliogenesis. We established the first etiological basis of STAR syndrome caused by CycQ mutations, and we contributed to the description of a new syndrome (Al Kaissi) caused by CDK10 mutations. In addition, we have developed a screening assay and identified the first molecules inhibiting CDK10/CycQ kinase activity.

We continue the study of the functions of CDK10 / CycQ mainly according to 4 approaches: i) Identification of interaction partners of CDK10 and CycQ; ii) Functional characterization of CDK10 and CycQ variants involved in Al Kaissi and STAR syndromes; iii) Biological chemistry approach, aiming to selectively inhibit CDK10 by small chemical molecules (iv) Knockout of the CDK10 gene by CRISPR in immortalized human cells.

Project leader: Pierre Colas – CR INSERM ( )

People involved: Sabine Genicot – IR CNRS; Thomas Robert – IE CNRS; Anne-Catherine Dock-Bregeon – DR CNRS Emérite

Former members: Vincent Guen (Master and PhD 2010-2013); Amel Hamdi (PhD and Post-Doc 2009-2013); Carly Gamble (Post-Doc 2011-2014)

Publications:

- Robert T, Dock-Bregeon AC, Colas P. (2021) “Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders” Mol Genet Genomic Med.

- Colas P. (2020) “Cyclin-dependent kinases and rare developmental disorders”. Orphanet J Rare Dis

- Robert T, Johnson JL, Guichaoua R, Yaron TM, Bach S, Cantley LC, Colas P. (2020) “Development of a CDK10/CycM in vitro kinase screening assay and identification of first small-molecule inhibitors”. Front Chem.

- Guen VJ, Edvardson S, Fraenkel ND, Fattal-Valevski A, Jalas C, Anteby I, Shaag A, Dor T, Gillis D, Kerem E, Lees JA, Colas P, Elpeleg O. (2018) “ A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness.” Am J Med Genet.

- Guen VJ, Gamble C, Lees JA, Colas P. (2017) “The awakening of the CDK10/Cyclin M protein kinase” Oncotarget

- Guen VJ, Gamble C, Perez DE, Bourassa S, Zappel H, Gärtner J, Lees JA, Colas P. (2016) “STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis.” Cell Cycle.

- Guen V, Gamble C, Flajolet M, Unger S, Thollet A, Ferandin Y, Superti-Furga A, Cohen PA, Meijer L, Colas P. (2013) “CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome”. Proc Natl Acad Sci USA.