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Fujinaga, Koh; Huang, Fang; Peterlin, B. Matija
Molecular cell, 02/2023, Letnik: 83, Številka: 3Journal Article
The positive transcription elongation factor b (P-TEFb) is composed of cyclins T1 or T2 and cyclin-dependent kinase 9 that regulate the elongation phase of transcription by RNA polymerase II. By antagonizing negative elongation factors and phosphorylating the C-terminal domain of RNA polymerase II, P-TEFb facilitates the elongation and co-transcriptional processing of nascent transcripts. This step is critical for the expression of most eukaryotic genes. In growing cells, P-TEFb is regulated negatively by its reversible associations with HEXIM1/2 in the 7SK snRNP and positively by a number of transcription factors, as well as the super elongation complex. In resting cells, P-TEFb falls apart, and cyclin T1 is degraded by the proteasome. This complex regulation of P-TEFb has evolved for the precise temporal and spatial regulation of gene expression in the organism. Its dysregulation contributes to inflammatory and neoplastic conditions. P-TEFb promotes transcription elongation by releasing the pause of RNAPII. Research on P-TEFb has expanded our understanding of eukaryotic transcription and diseases such as AIDS and cancer. In this review, Fujinaga et al. focus on the structure, function, and regulation of P-TEFb.
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