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The roles of cyclin‐dependent kinase 11 (CDK11) during mammalian development
Author(s) -
Li Tongyuan,
Inoue Akira,
Kidd Vincent,
Lahti Jill
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a461
Subject(s) - biology , rna splicing , microbiology and biotechnology , mitosis , kinase , alternative splicing , internal ribosome entry site , transcription (linguistics) , messenger rna , gene , translation (biology) , genetics , rna , linguistics , philosophy
CDK11 gene encodes two proteins, p110 and p58. CDK11 p110 proteins are part of large‐molecular‐weight complexes containing RNA polymerase II, transcriptional elongation and general pre‐mRNA splicing factors, suggesting they couple transcription and pre‐mRNA splicing. CDK11 p58 is expressed only during G2/M from an internal ribosome entry site (IRES) present in the mRNA encoding CDK11 p110 and appears to regulate mitosis. To examine the in vivo role of CDK11 p110/p58 kinases, we generated CDK11 p110/p58 ‐null mice and found CDK11 p110/p58 deficiency results in early embryonic lethality and apoptosis between E3.5 and E4.0. Cells within CDK11 p110/p58−/− embryos exhibit both proliferative defects and a mitotic arrest. These results indicated that the CDK11 p110/p58 kinases are essential for cellular viability and normal early embryonic development. CDK11 p110/p58 T cell‐specific knockout mice generated by using Cre/loxP system show defects in T cell development. Deletion of CDK11 p110/p58 in thymocytes results in a block at the double negative (DN) stage due to the defective pre‐TCR signaling, impaired proliferation and apoptosis. CDK11 p110/p58 deficiency in thymocytes also affects alternative splicing of CD45. Taken together, these results indicate that CDK11 protein kinases play important roles in transcription, splicing and mitotic regulation. (Supported by NIH grants GM44088, CA0211765, and ALSAC)