WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice.
BACKGROUND
WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood.


METHODS
In the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon. Further, we have used human colon cancer cell lines, HT29 and COLO205, and mouse primary embryonic fibroblast to understand the molecular mechanism of WDR13 action.


RESULTS
We observed that mice lacking Wdr13 gene have reduced number of tumors and are more susceptible to DSS-induced colon ulcers. We also show that WDR13 is a part of multi protein complex c-Jun/NCoR1/HDAC3 and it acts as a transcriptional activator of AP1 target genes in the presence of JNK signal. Consistent with in vitro data, we observed reduced expression of AP1 target genes in colon after AOM/DSS treatment in Wdr13 knockout mice as compared to that in wild type.


CONCLUSION
Mice lacking Wdr13 gene showed reduced expression of AP1 target genes and protection from colitis-induced colorectal tumors.
['Singh|Vijay Pratap|VP|', 'Katta|Saritha|S|', 'Kumar|Satish|S|']
D000818:Animals D001397:Azoxymethane D018797:Cell Cycle Proteins D002460:Cell Line D003092:Colitis D003110:Colonic Neoplasms D016264:Dextran Sulfate D004195:Disease Models, Animal D015972:Gene Expression Regulation, Neoplastic D057809:HEK293 Cells D019073:HT29 Cells D006706:Homeostasis D006801:Humans D061986:MCF-7 Cells D051379:Mice D009687:Nuclear Proteins D016755:Proto-Oncogene Proteins c-jun D015398:Signal Transduction
c-Jun Colon Transcriptional activator JNK signalling Apoptosis