Title:The Emerging Picture of CDK11: Genetic, Functional and Medicinal Aspects
Volume: 25
Issue: 8
Author(s): Nikolas Ferreira dos Santos Paparidis and Fernanda Canduri*
Affiliation:
- Department of Chemistry and Molecular Physics, Institute of Chemistry of Sao Carlos, Sao Paulo University, Av. Trabalhador Saocarlense, 400, Zip Code 780, 13560-970, Sao Carlos-SP,Brazil
Keywords:
CDK11, PITSLRE, RNAPII transcription, spindle assembly, sister-chromatid cohesion, pro-apoptotic
signaling.
Abstract: Cyclin-dependent kinase 11 is a relatively neglected member of the transcriptional
CDKs subfamily, despite possibly being the most versatile CDK in this group. Different
CDK11 variants are known to play essential roles in major cellular processes as
mRNA transcription (CDK11p110), mitosis (CDK11p58), and apoptosis (CDK11p46 and
CDK11p60). Each CDK11 species targets a particular set of substrates related to its functional
background, but all isoforms originate from the CDC2L gene complex in human
chromosome 1p36.2. CDK11p110 is synthesized through regular cap-dependent translation
of CDK11 mRNA, whereas CDK11p58 translation is initiated through an IRES, and
occurs only at G2 and M phases. CDK11p46 and CDK11p60, in turn, are the products of
caspase cleavage of the larger isoforms during apoptosis. L-type cyclins are the main
partners of CDK11, although CDK11p58 species interacts specifically with cyclin D3.
The link between CDK11 dysfunction and cancer has been known for a long time, and
critical roles in the proliferation of different cancer cell lines have been assigned to
CDK11. This review summarizes more than 25 years of studies that unraveled CDK11
genetic and functional aspects.
