We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A novel ubiquitin–proteasome system regulation of Sgf73/ataxin-7 that maintains the integrity of the coactivator SAGA in orchestrating transcription.
- Authors
Barman, Priyanka; Kaja, Amala; Chakraborty, Pritam; Guha, Shalini; Roy, Arpan; Ferdoush, Jannatul; Bhaumik, Sukesh R.
- Abstract
Ataxin-7 maintains the integrity of Spt-Ada-Gcn5-Acetyltransferase (SAGA), an evolutionarily conserved coactivator in stimulating preinitiation complex (PIC) formation for transcription initiation, and thus, its upregulation or downregulation is associated with various diseases. However, it remains unknown how ataxin-7 is regulated that could provide new insights into disease pathogenesis and therapeutic interventions. Here, we show that ataxin-7’s yeast homologue, Sgf73, undergoes ubiquitylation and proteasomal degradation. Impairment of such regulation increases Sgf73’s abundance, which enhances recruitment of TATA box-binding protein (TBP) (that nucleates PIC formation) to the promoter but impairs transcription elongation. Further, decreased Sgf73 level reduces PIC formation and transcription. Thus, Sgf73 is fine-tuned by ubiquitin–proteasome system (UPS) in orchestrating transcription. Likewise, ataxin-7 undergoes ubiquitylation and proteasomal degradation, alteration of which changes ataxin-7’s abundance that is associated with altered transcription and cellular pathologies/diseases. Collectively, our results unveil a novel UPS regulation of Sgf73/ataxin-7 for normal cellular health and implicate alteration of such regulation in diseases.
- Subjects
PROTEINS; GENETICS; NERVE tissue proteins; PROTEOLYTIC enzymes; RESEARCH funding
- Publication
Genetics, 2023, Vol 224, Issue 3, p1
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1093/genetics/iyad071