Animals
Animals, Genetically Modified
Apoptosis
/ genetics
Breast
/ pathology
Breast Neoplasms
/ genetics
Cell Line, Tumor
DNA-Binding Proteins
/ genetics
Drosophila Proteins
/ genetics
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Models, Animal
Protein Stability
Proto-Oncogene Proteins c-myc
/ genetics
RNA-Seq
Tissue Array Analysis
Transcription Factors
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Ubiquitination
/ genetics
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
29
05
2019
revised:
21
11
2019
accepted:
28
01
2020
pubmed:
8
2
2020
medline:
21
10
2020
entrez:
8
2
2020
Statut:
ppublish
Résumé
For maximal oncogenic activity, cellular MYC protein levels need to be tightly controlled so that they do not induce apoptosis. Here, we show how ubiquitin ligase UBR5 functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 ubiquitinates MYC and its effects on MYC protein stability are independent of FBXW7. Silencing of endogenous UBR5 induced MYC protein expression and regulated MYC target genes. Consistent with the tumor suppressor function of UBR5 (HYD) in Drosophila, HYD suppressed dMYC-dependent overgrowth of wing imaginal discs. In contrast, in cancer cells, UBR5 suppressed MYC-dependent priming to therapy-induced apoptosis. Of direct cancer relevance,
Identifiants
pubmed: 32029551
pii: 0008-5472.CAN-19-1647
doi: 10.1158/0008-5472.CAN-19-1647
doi:
Substances chimiques
DNA-Binding Proteins
0
Drosophila Proteins
0
MYC protein, human
0
Myc protein, Drosophila
0
Proto-Oncogene Proteins c-myc
0
Transcription Factors
0
UBR5 protein, human
EC 2.3.2.26
hyd protein, Drosophila
EC 2.3.2.26
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1414-1427Informations de copyright
©2020 American Association for Cancer Research.