SEPT9_i1 is required for the association between HIF-1α and importin-α to promote efficient nuclear translocation.

ABSTRACT: Septin 9 isoform 1 (SEPT9_i1) protein associates with hypoxia-inducible factor (HIF)-1α to augment HIF-1 transcriptional activity. The first 25 amino acids of SEPT9_i1 (N 25) are unique compared with other members of the mammalian septin family. This N 25 domain is critical for HIF-1 activation by SEPT9_i1 but not essential for the protein-protein interaction. Here, we show that expression of N 25 induces a significant dose-dependent inhibition of HIF-1 transcriptional activity under normoxia and hypoxia without influencing cellular HIF-1α protein levels. In vivo, N 25 expression inhibits proliferation, tumor growth and angiogenesis concomitant with decreased expression levels of intratumoral HIF-1 downstream genes. Depletion of endogenous SEPT9_i1 or the exogenous expression of N 25 fragm

SUBMITTER: Golan M 

PROVIDER: S-EPMC3755080 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature