Factor acetyltransferase activity associated with several histone acetyltransferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transactivator protein, Tat. The interaction between Tat and hGCN5 is direct and involves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the protein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p300/CBP has been recently shown to stimulate Tat transcriptional activity and accordingly, we have found that hGCN5 can considerably enhance Tat-dependent transcription of the HIV-1 long terminal repeat. These data highlight the importance of the acetylation of lysines 50 and 51 in the function of Tat, since different histone acetyltransferases involved in distinct signaling pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.
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http://dx.doi.org/10.1074/jbc.M101385200 | DOI Listing |
Psychiatr Genet
February 2025
Department of Obstetrics.
Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant genetic disease characterized by growth retardation, psychomotor retardation, and distinctive facial features. It is primarily caused by mutations in CREBBP or EP300. In this study, we aimed to describe the clinical manifestations and genetic analyses of two cases with RSTS.
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January 2025
Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
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Nat Commun
January 2025
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Univ. Montpellier, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.
Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U).
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Department of Pediatric Metabolism and Nutrition, Gazi University, Ankara, Türkiye.
Cell Mol Life Sci
December 2024
Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Over the past few decades, microtubules have been targeted by various anticancer drugs, including paclitaxel and eribulin. Despite their promising effects, the development of drug resistance remains a challenge. We aimed to define a novel cell death mechanism that targets microtubules using eribulin and to assess its potential in overcoming eribulin resistance.
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