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[Misregulation of P-TEFb activity: pathological consequences].

Abstract
P-TEFb stimulates transcription elongation by phosphorylating the carboxy-terminal domain of RNA pol II and antagonizing the effects of negative elongation factors. Its cellular availability is controlled by an abundant non coding RNA, conserved through evolution, the 7SK RNA. Together with the HEXIM proteins, 7SK RNA associates with and sequesters a fraction of cellular P-TEFb into a catalytically inactive complex. Active and inactive forms of P-TEFb are kept in a functional and dynamic equilibrium tightly linked to the transcriptional requirement of the cell. Importantly, cardiac hypertrophy and development of various types of human malignancies have been associated with increased P-TEFb activity, consequence of a disruption of this regulatory equilibrium. In addition, the HIV-1 Tat protein also releases P-TEFb from the 7SK/HEXIM complex during viral infection to promote viral transcription and replication. Here, we review the roles played by the 7SK RNP in cancer development, cardiac hypertrophy and AIDS.
AuthorsLisa Muniz, Tamàs Kiss, Sylvain Egloff
JournalMeĢdecine sciences : M/S (Med Sci (Paris)) Vol. 28 Issue 2 Pg. 200-5 (Feb 2012) ISSN: 0767-0974 [Print] France
Vernacular TitlePerturbations de la transcription liées à une dérégulation de P-TEFb : cancer, Sida et hypertrophie cardiaque.
PMID22377309 (Publication Type: English Abstract, Journal Article, Review)
Copyright© 2012 médecine/sciences – Inserm / SRMS.
Chemical References
  • HEXIM1 protein, human
  • RNA-Binding Proteins
  • Positive Transcriptional Elongation Factor B
Topics
  • Cardiomegaly (genetics, metabolism)
  • Disease (etiology, genetics)
  • Enzyme Activation (genetics, physiology)
  • Gene Expression Regulation (genetics)
  • HIV-1 (metabolism, physiology)
  • Humans
  • Models, Biological
  • Neoplasms (genetics, metabolism)
  • Positive Transcriptional Elongation Factor B (genetics, metabolism, physiology)
  • RNA-Binding Proteins (metabolism, physiology)
  • Transcription, Genetic (genetics)

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