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Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.
- Source :
-
The Journal of cell biology [J Cell Biol] 2024 Nov 04; Vol. 223 (11). Date of Electronic Publication: 2024 Aug 28. - Publication Year :
- 2024
-
Abstract
- The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells.<br /> (© 2024 Huang et al.)
- Subjects :
- Humans
Ubiquitin-Protein Ligases metabolism
Ubiquitin-Protein Ligases genetics
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Pancreatic Neoplasms genetics
HEK293 Cells
Protein Processing, Post-Translational
Protein Stability
Cell Line, Tumor
Proteolysis
Proteasome Endopeptidase Complex metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics
Lysosomes metabolism
Autophagy
Ubiquitination
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 223
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 39196068
- Full Text :
- https://doi.org/10.1083/jcb.202308099