Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
p53 is the most intensively studied
tumour suppressor
1
. The regulation of p53 homeostasis is essential for its tumour-suppressive function
2,3
. Although p53 is regulated by an array of post-translational modifications, both during normal homeostasis and in stress-induced responses
2-4
, how p53 maintains its homeostasis remains unclear. UFMylation is a recently identified ubiquitin-like modification with essential biological functions
5-7
. Deficiency in this modification leads to embryonic lethality in mice and disease in humans
8-12
. Here, we report that p53 can be covalently modified by UFM1 and that this modification stabilizes p53 by antagonizing its ubiquitination and proteasome degradation. Mechanistically, UFL1, the UFM1 ligase
6
, competes with MDM2 to bind to p53 for its stabilization. Depletion of UFL1 or
DDRGK1
, the critical regulator of UFMylation
6,13
, decreases p53 stability and in turn promotes cell growth and tumour formation in vivo. Clinically, UFL1 and
DDRGK1
expression are downregulated and positively correlated with levels of p53 in a high percentage of renal cell carcinomas. Our results identify UFMylation as a crucial post-translational modification for maintenance of p53 stability and tumour-suppressive function, and point to UFMylation as a promising therapeutic target in cancer.
...
PMID:UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. 3280 1
