Sci. STKE, 4 March 2003
Transcription Linking Microtubule Dynamics to HIF-1α
Cells call upon the transcription factor nuclear factor kappa B (NF-B) to alter gene expression in response to stressful conditions. Although cytoskeletal reorganization is a normal and dynamic process, disruption of microtubules correlates with increased NF-B activity as well. Jung et al. report that this correlation can be further linked to increased expression of the transcription factor hypoxia-inducible factor-1 alpha (HIF-1α). HIF-1α activity is regulated by the ubiquitin-proteasome pathway. Hypoxic conditions prevent its destruction, allowing HIF-1α to enter the nucleus and activate genes that promote cell survival. When a variety of mammalian cells were treated with microtubule-depolymerizing agents (MDAs), NF-B activity and HIF-1α protein expression increased. Inhibition of NF-B with drugs or by expression of a repressor protein blocked this effect, and other transcription factors did not mediate the effect of MDAs on HIF-1α. A cell line that is resistant to the disrupting effect of MDAs displayed normal NF-B activity but was unable to raise HIF-1α expression in response to MDA treatment. Transcription inhibitors also blocked the effect of MDAs on HIF-1α expression, indicating that this nonhypoxic signaling pathway between microtubules and the gene targets of HIF-1α is distinct from the hypoxia-induced pathway that regulates HIF-1α stability, and could participate in cytoskeletal remodeling during normal and tumorigenic processes.
Y.-J. Junh, J.S. Isaacs, S. Lee, J. Trepel, L. Neckers, Microtubule disruption utilizes an NFB-dependent pathway to stabilize HIF-1α protein. J. Biol. Chem. 278, 7445-7452 (2003). [Abstract] [Full Text]
Citation: Linking Microtubule Dynamics to HIF-1α. Sci. STKE 2003, tw91 (2003).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882