WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice

BMC Cancer

Research Article

Vijay Pratap Singh¹  Satish Kumar¹  Saritha Katta¹ 

[1] National Facility for Transgenic and Gene Knockout Mice, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, 500007, Hyderabad, India;

关键词: JNK signalling;    c-Jun;    Apoptosis;    Colon;    Transcriptional activator;   

DOI  :  10.1186/s12885-017-3118-7

 received in 2015-11-26, accepted in 2017-02-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWDR13 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.MethodsIn 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.ResultsWe 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.ConclusionMice lacking Wdr13 gene showed reduced expression of AP1 target genes and protection from colitis-induced colorectal tumors.

【 授权许可】

CC BY   
© The Author(s). 2017