The ubiquitin ligase UBE3A dampens ERK pathway signalling in HPV E6 transformed HeLa cells.

ABSTRACT: Signalling through the ERK MAP kinase pathway plays an important role in many biological processes and it is often deregulated in disease states such as cancer. One major effect of MAP kinase signalling is to promote gene expression through the phosphorylation and activation of transcription factors like ELK1. ELK1 in turn controls the activity of immediate-early genes such as FOS. Here we have used ELK1 activation in HeLa cells as a read out to conduct a genome-wide siRNA screen to identify negative regulators of ERK-mediated immediate-early gene activation. One of the candidates that we identified was the E3 ubiquitin ligase UBE3A/E6-AP. Reductions in UBE3A levels cause increased basal levels of ERK activity, a loss of growth factor-mediated ERK activation and concomitant defects in imme

SUBMITTER: Aguilar-Martinez E 

PROVIDER: S-EPMC4376912 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature