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Catalytic activity of Cdk9 is required for nuclear co‐localization of the Cdk9/cyclin T1 (P‐TEFb) complex
Author(s) -
Napolitano Giuliana,
Majello Barbara,
Lania Luigi
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10376
Subject(s) - p tefb , cyclin dependent kinase 9 , rna polymerase ii , nuclear localization sequence , nuclear export signal , elongation factor , microbiology and biotechnology , biology , subcellular localization , cell nucleus , chemistry , phosphorylation , cyclin dependent kinase 2 , protein kinase a , biochemistry , rna , gene expression , nucleus , gene , cytoplasm , ribosome , promoter
Cdk9 and its binding partner cyclin T1 comprise the positive elongation factor b (P‐TEFb). P‐TEFb phosphorylates the RNA polymerase II carboxyl‐terminal‐domain (CTD) allowing efficient transcription elongation. Recent studies showed that Cdk9 is a predominant nuclear protein, and here we investigated the functional requirement for nuclear localization of Cdk9. We found that the catalytic inactive kinase mutant (Cdk9dn) fails to accumulate in the nucleus showing a diffuse sub‐cellular localization. In addition to the catalityc activity, nuclear localization of Cdk9 protein requires the presence of the phospho‐acceptor sites at the C‐terminus tail. Finally, enforced expression of wild‐type cyclinT1, which enhances nuclear localization of Cdk9wt, fails to direct the Cdk9 mutants to the nucleus. Collectively, these findings implicate that nuclear localization of Cdk9 requires auto‐phosphorylation of the kinase, and highlight the presence of a regulatory mechanism underlying the nuclear localization of the P‐TEFb complex. J. Cell. Physiol. 197: 1–7, 2003© 2003 Wiley‐Liss, Inc.