Regulation of eIF2 α by RNF4 promotes melanoma tumorigenesis and therapy resistance

Among the hallmarks of melanoma, are impaired proteostasis and the rapid development of resistance to targeted therapy, that represent a major clinical challenge. However, the molecular machinery that links these processes is unknown. Here we describe that by stabilizing key melanoma oncoproteins the ubiquitin ligase RNF4 promotes tumorigenesis and confers resistance to targeted therapy in melanoma cells, xenograft mouse models and patient samples. In patients, RNF4 protein and mRNA levels correlate with poor prognosis and with resistance to MAPK inhibitors.

Source: Journal of Investigative Dermatology - April 28, 2020 Category: Dermatology Authors: Emily Avitan-Hersh, Yongmei Feng, Avital Oknin Vaisman, Yamen Abu Ahmed, Yaniv Zohar, Tongwu Zhang, Joo Sang Lee, Ikrame Lazar, Saeed Sheikh Khalil, Yulia Feiler, Harriet Kluger, Chaim Kahana, Kevin Brown, Eytan Ruppin, Ze ’ev A. Ronai, Amir Orian Tags: Original Article Source Type: research