P-TEFb and Brd4: actors of the transcription pause release as therapeutical targets

• Published in: M.S. Médecine sciences Vol. 34; no. 8-9; pp. 685 - 692
• Main Authors: Furlan, Alessandro, Agbazahou, Florence, Henry, Mélanie, Gonzalez-Pisfil, Mariano, Le Nézet, Corentin, Champelovier, Dorian, Fournier, Marie, Vandenbunder, Bernard, Bidaux, Gabriel, Héliot, Laurent
• Format: Journal Article
• Language: French
• Published: France 01.08.2018
• Subjects: Humans; Molecular Targeted Therapy - methods; Nuclear Proteins - physiology; Positive Transcriptional Elongation Factor B - physiology; RNA Polymerase II - metabolism; Transcription Factors - physiology; Transcription, Genetic - physiology
• ISSN: 1958-5381
• DOI: 10.1051/medsci/20183408015

Most cell physiology events are dictated by the integration of perceived signals and the elaboration by cells of adapted answers via the execution of proper transcriptional programs. In order to ensure an optimal control of these answers, many regulation mechanisms have been selected throughout the evolution, thus allowing to fine-tune transcript expression. The transcriptional pause and its release by P-TEFb (Positive Transcription Elongation Factor) have been evidenced two decades ago. Since then, the importance of such mechanisms has been highlighted by the association between alterations of this machinery and the appearance of diseases. P-TEFb and Brd4 have thus recently emerged as potential therapeutical targets for cancers and AIDS notably. In this review, we present a brief case history and an up-to-date synthesis of models for transcriptional pause release. We later discuss on the pathophysiological processes associated with this mechanism and clinical trials targeting Brd4 and P-TEFb.