Kinome-wide functional genomics screen reveals a novel mechanism of TNFα-induced nuclear accumulation of the HIF-1α transcription factor in cancer cells.

ABSTRACT: Hypoxia-inducible factor-1 (HIF-1) and its most important subunit, HIF-1α, plays a central role in tumor progression by regulating genes involved in cancer cell survival, proliferation and metastasis. HIF-1α activity is associated with nuclear accumulation of the transcription factor and regulated by several mechanisms including modulation of protein stability and degradation. Among recent advances are the discoveries that inflammation-induced cytokines and growth factors affect protein accumulation of HIF-1α under normoxia conditions. TNFα, a major pro-inflammatory cytokine that promotes tumorigenesis is known as a stimulator of HIF-1α activity. To improve our understanding of TNFα-mediated regulation of HIF-1α nuclear accumulation we screened a kinase-specific siRNA library using a cell

SUBMITTER: Schoolmeesters A 

PROVIDER: S-EPMC3280275 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature