CrkL is a Co-Activator of Estrogen Receptor α That Enhances Tumorigenic Potential in Cancer

摘要: Signaling via estrogen receptor (ER) occurs by interacting with many proteins. Nuclear interactome analysis of ERα in an embryo implantation model revealed the association chicken tumor virus no. 10 regulator kinase like (CrkL) ERα, which was further validated mammalian two-hybrid assay as well coimmunoprecipitation and colocalization. Mutation LPALL motif CrkL disrupts ERα-CrkL interaction its transactivation potential, thereby suggesting that is mediated single ER binding motif, Leu-Pro-Ala-Leu-Leu (LXXLL) sarcoma homology (SH)2 domain. deletion constructs SH2 domain target to nucleus due presence nuclear localization signal. Interestingly, SH2-SH3 (N terminal) construct shows increased potential CrkI. Weak capability mutated ERα-Y538F validates interacts YDLL at Tyr 541. In attempt understand physiological relevance this association, we investigated impact on cell proliferation using a cancer model, because events associated process pregnancy are analogous. Also, overexpression frequently tumorigenesis. However, significance hormone-regulated cancers still remains obscure. Here, demonstrate directly enhances tumorigenic CrkL, thus pointing role proliferation. human endometrial cancers, observed strong between levels. Thus, molecular signaling set off may have central cancer, two share parallels growth, invasion, immune tolerance.