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TIP30 has an intrinsic kinase activity required for up‐regulation of a subset of apoptotic genes
Author(s) -
Xiao Hua,
Palhan Vikas,
Yang Yili,
Roeder Robert G.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.5.956
Subject(s) - biology , library science , computer science
CC3 is a metastasis suppressor that inhibits metastasis of the variant small cell lung carcinoma (v‐SCLC) by predisposing cells to apoptosis. The same protein was also reported as a cellular cofactor, TIP30, which stimulates HIV‐1 Tat‐activated transcription by interacting with both Tat and RNA polymerase II. We report here that TIP30/CC3 is a novel serine/threonine kinase. It phosphorylates the heptapeptide repeats of the C‐terminal domain (CTD) of the largest RNA polymerase II subunit in a Tat‐dependent manner. Amino acid substitutions in the putative ATP binding motif that abolish the TIP30 kinase activity also inhibit the ability of TIP30 to enhance Tat‐activated transcription or to sensitize NIH 3T3 and v‐SCLC cells to apoptosis. Furthermore, ectopic expression of TIP30/CC3 in v‐SCLC cells induces expression of a number of genes that include the apoptosis‐related genes Bad and Siva, as well as metastasis suppressor NM23‐H2. These data demonstrate a molecular mechanism for TIP30/CC3 function and suggest a novel pathway for regulating apoptosis.