Journal
CANCER RESEARCH
Volume 66, Issue 20, Pages 9870-9877Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-1679
Keywords
-
Categories
Funding
- NCI NIH HHS [P01CA19014] Funding Source: Medline
Ask authors/readers for more resources
Hypoxia-inducible factor 1 (HIF1) is up-regulated in most malignant tumors usually via interruption of ubiquitination and proteasomal degradation of its subunit alpha. Recently, we have shown that the principal ERV oncoprotein, latent membrane protein 1 (LMP1), activates HIF1 alpha and subsequently expression of HIFI-responsive genes in epithelial cells. Here, we explore the mechanism for HIF1 alpha activation by LMP1 in nasopharyngeal epithelial cells: LMP1 up-regulates the level of Siah1 E3 ubiquitin ligase by enhancing its stability, which subsequently induces proteasomal degradation of prolyl HIF-hydroxylases 1 and 3 that normally mark HIF1 alpha for degradation. As a result, LMP1 prevents formation of von Hippel-Lindau/HIF1 alpha complex, as shown by coimmunoprecipitation analyses. Thus, Siah1 is implicated in the regulation of HIF1 alpha and is involved in a recently appreciated aspect of ERV-mediated tumorigenesis, namely, the angiogenesis process triggered by LMP1.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available