Affiliations
- Laboratory of Molecular Neuroscience, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, 344090, Russia.
- Department of General and Clinical Biochemistry No.2, Rostov State Medical University, 29 Nakhichevansky Lane, Rostov-on-Don, 344022, Russia.
- Laboratory of Molecular Neuroscience, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, 344090, Russia. svdemyanenko@sfedu.ru.
PMID: 38546874 DOI: 10.1007/s12017-024-08777-2
Abstract
Background: This study investigates the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While c-Myc’s involvement in cell death and survival is known, its post-translational modifications, particularly acetylation, remain underexplored in ischemia models.
Methods: We examined c-Myc expression in perifocal cells during stroke recovery to explore its regulatory mechanisms via acetylation. Molecular dynamics simulations were used to assess the impact of lysine 148 on c-Myc’s spatial structure.
Results: In peri-infarct neurons, c-Myc is upregulated with acetylation at K148 but not K323. Increased acetylation at K148 reduces c-Myc compaction, potentially limiting its nuclear penetration, promoting calpain-mediated cleavage, and decreasing nuclear localization. Cytoplasmic acetylation at K148 may alter c-Myc's interaction with unidentified proteins, influencing its pro-apoptotic effects and promoting cytoplasmic accumulation.
Conclusion: Targeting SIRT2, which primarily affects K148 acetylation, could be a promising avenue for future stroke therapy strategies.
Keywords: Acetylation; Molecular dynamics simulation; Penumbra; Photothrombotic stroke; c-Myc.
