A Cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to Hexim1 and HIV tat.

Background: The positive transcription elongation factor b (P-TEFb) plays an essential role in activating HIV genome transcription. It is recruited to the HIV LTR promoter through an interaction between the Tat viral protein and its Cyclin T1 subunit. P-TEFb activity is inhibited by direct binding of its subunit Cyclin T (1 or 2) with Hexim (1 or 2), a cellular protein, bound to the 7SK small nuclear RNA.

Ubiquitination of HEXIM1 by HDM2.

Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is an inhibitor of the positive transcription elongation factor b (P-TEFb), which controls RNA polymerase II transcription and human immunodeficiency virus Tat transactivation. In cells, more than half of P-TEFb is associated with HEXIM1 resulting in the inactivation of P-TEFb. Recently, we found that nucleophosmin (NPM), a key factor involved in p53 signaling pathway, interacts with HEXIM1 and activates P-TEFb-dependent transcription.

7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor.

Human 7SK RNA is an abundant 331 nt nuclear transcript generated by RNA polymerase III. Binding of 7SK RNA to HEXIM1/2 turns these proteins into inhibitors of P-TEFb (Positive Transcriptional Elongation Factor b). P-TEFb is required for RNA polymerase II transcription elongation.