Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast
- 1Harvard Medical School, Department of Cell Biology, Howard Hughes Medical Institute
Abstract
Membrane fluidity depends on unsaturated acyl chains that are generated in Saccharomyces cerevisiae by the desaturase Ole1, whose expression is primarily under the control of the transcription factor Mga2. Here, we show that the endoplasmic reticulum-anchored Mga2 precursor is ubiquitinated by the E3 ligase Rsp5 and then processively degraded by the proteasome until proteolysis stalls at a defined site, releasing a soluble fragment that enters the nucleus and activates Ole1 transcription. Unexpectedly, Mga2 contains a DNA-binding domain and a trans-activation-like segment structurally and functionally related to those of the human tumor suppressor p53. The mature transcription factor is degraded in the nucleus in a DNA binding-dependent manner; blocking this degradation causes unsaturated acyl chains to accumulate in lipid droplets, a detoxification response required for cell viability. These findings define the pathways that activate and inactivate Mga2, and uncover an evolutionary connection between the yeast lipid homeostasis regulator Mga2 and p53.
Related
- Mechanistic insights into proteolytic activation ofmembrane-bound NAC transcription factor SlNACMTF3 intomato plants under heat stress
- Molecular mechanism of albicidin-dependent transcription activation by the antibiotic resistance factor AlbA
- Light-dependent activation of TCP4 by the GATA25 transcription factor promotes petiole and hypocotyl elongation in Arabidopsis thaliana
- Transcriptional activation of AaAGPase by AaGLK transcription factor determines ascorbic acid levels in kiwifruit
- Constitutively-active Positive Transcription Factor b (P-TEFb) prevents viral latency.
BibTeX
@misc{wan2026activation,
title = {{Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast}},
author = {N. Wan and J. Kuklewicz and J. A. Paulo and C. Nardone and S. P. Gygi and T. A. Rapoport},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748402},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748402v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast
AU - N. Wan
AU - J. Kuklewicz
AU - J. A. Paulo
AU - C. Nardone
AU - S. P. Gygi
AU - T. A. Rapoport
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748402
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748402v1
AB - Membrane fluidity depends on unsaturated acyl chains that are generated in Saccharomyces cerevisiae by the desaturase Ole1, whose expression is primarily under the control of the transcription factor Mga2. Here, we show that the endoplasmic reticulum-anchored Mga2 precursor is ubiquitinated by the E3 ligase Rsp5 and then processively degraded by the proteasome until proteolysis stalls at a defined site, releasing a soluble fragment that enters the nucleus and activates Ole1 transcription. Unexpectedly, Mga2 contains a DNA-binding domain and a trans-activation-like segment structurally and functionally related to those of the human tumor suppressor p53. The mature transcription factor is degraded in the nucleus in a DNA binding-dependent manner; blocking this degradation causes unsaturated acyl chains to accumulate in lipid droplets, a detoxification response required for cell viability. These findings define the pathways that activate and inactivate Mga2, and uncover an evolutionary connection between the yeast lipid homeostasis regulator Mga2 and p53.
ER -