SART1 antibody

Background of SART1 antibody

SART1 (HAF, Ara1, HOMS1, Snu66) is part of the SNU66/SART1 family. This protein is subject to phosphorylation, and sumoylation by SUMO2. It is highly expressed in the nucleus of highly proliferative cells, but is also expressed in the cytosol of epithelial cancers. HAF is a transcription factor that enhances hypoxia inducible factor 1 (HIF-1)-induced activation in VEGF and EPO genes under hypoxic conditions (http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/409-d). SART1/HAF is up-regulated in a multitude of tumors. During long periods of hypoxia, its level increases, but the levels are decreased during acute hypoxia. A recent study showed that SART1/HAF is an E3 ubiquitin ligase that binds and ubiquitites HIF-1 alpha by an oxygen and pVHL-independent mechanism, which then targets HIF-1 alpha for proteasomal degradation. SART1/HAF also binds HIF-2 alpha at a separate site and increases HIF-2 alpha transactivation without triggering degradation. Therefore, HAF is able to alter the response of cancer cells from HIF-1 alpha-dependent to HIF-2 alpha-dependent transcription and initiates genes involved in invasion such as MMP9, PAI-1, and the stem cell factor OCT-3/4. The shift to HIF-2 alpha dependent gene expression instigated by HAF also promotes an enhanced tumor stem cell population, which results in extremely aggressive tumors in vivo. SART1/HAF presents a method for more aggressive tumor growth under sustained hypoxia (PMID: 21512133; 18838541; 19377289)