CREPT/RPRD1B promotes tumorigenesis through STAT3-driven gene transcription in a p300-dependent manner.
Br J Cancer
; 124(8): 1437-1448, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33531691
ABSTRACT
BACKGROUND:
Signal transducer and activator of transcription 3 (STAT3) has been shown to upregulate gene transcription during tumorigenesis. However, how STAT3 initiates transcription remains to be exploited. This study is to reveal the role of CREPT (cell cycle-related and elevated-expression protein in tumours, or RPRD1B) in promoting STAT3 transcriptional activity.METHODS:
BALB/c nude mice, CREPT overexpression or deletion cells were employed for the assay of tumour formation, chromatin immunoprecipitation, assay for transposase-accessible chromatin using sequencing.RESULTS:
We demonstrate that CREPT, a recently identified oncoprotein, enhances STAT3 transcriptional activity to promote tumorigenesis. CREPT expression is positively correlated with activation of STAT3 signalling in tumours. Deletion of CREPT led to a decrease, but overexpression of CREPT resulted in an increase, in STAT3-initiated tumour cell proliferation, colony formation and tumour growth. Mechanistically, CREPT interacts with phosphorylated STAT3 (p-STAT3) and facilitates p-STAT3 to recruit p300 to occupy at the promoters of STAT3-targeted genes. Therefore, CREPT and STAT3 coordinately facilitate p300-mediated acetylation of histone 3 (H3K18ac and H3K27ac), further augmenting RNA polymerase II recruitment. Accordingly, depletion of p300 abolished CREPT-enhanced STAT3 transcriptional activity.CONCLUSIONS:
We propose that CREPT is a co-activator of STAT3 for recruiting p300. Our study provides an alternative strategy for the therapy of cancers related to STAT3.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Transformation, Neoplastic
/
Cell Cycle Proteins
/
E1A-Associated p300 Protein
/
STAT3 Transcription Factor
/
Neoplasm Proteins
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Br J Cancer
Year:
2021
Document type:
Article
Affiliation country:
China