Cyclin-dependent kinase 12

Definition:

Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors.

References:

[1]. Christian A Bösken, et al. The structure and substrate specificity of human Cdk12/Cyclin K. Nat Commun. 2014 Mar 24;5:3505. [Content Brief]

[2]. Elizabeth Iorns, et al. CRK7 modifies the MAPK pathway and influences the response to endocrine therapy. Carcinogenesis. 2009 Oct;30(10):1696-701. [Content Brief]

[3]. T K Ko, et al. CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles. J Cell Sci. 2001 Jul;114(Pt 14):2591-603. [Content Brief]

[4]. Bartlomiej Bartkowiak, et al. CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev. 2010 Oct 15;24(20):2303-16. [Content Brief]

[5]. Dalibor Blazek, et al. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. 2011 Oct 15;25(20):2158-72. [Content Brief]

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