Kunal Rai, Kadir C Akdemir, Lawrence N Kwong, Petko Fiziev, Chang-Jiun Wu, Emily Z Keung, Sneha Sharma, Neha S Samant, Maura Williams, Jacob B Axelrad, Amiksha Shah, Dong Yang, Elizabeth A Grimm, Michelle C Barton, Denai R Milton, Timothy P Heffernan, James W Horner, Suhendan Ekmekcioglu, Alexander J Lazar, Jason Ernst, Lynda Chin
UNLABELLED: Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling...
December 2015: Cancer Discovery