Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.1320815111/-/DCSupplemental
Title: Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response
Authors: Zheng, X.
Zhou, A.-X.
Rouhi, P.
Uramoto, H.
Borén, J.
Cao, Y.
Pereira, T.
Akyürek, L.M.
Poellinger, L. 
Keywords: Cancer
Signal transduction
Subcellular localization
Issue Date: 18-Feb-2014
Citation: Zheng, X., Zhou, A.-X., Rouhi, P., Uramoto, H., Borén, J., Cao, Y., Pereira, T., Akyürek, L.M., Poellinger, L. (2014-02-18). Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response. Proceedings of the National Academy of Sciences of the United States of America 111 (7) : 2560-2565. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.1320815111/-/DCSupplemental
Abstract: The cellular response to hypoxia is regulated by hypoxia-inducible factor-1a and -2a (HIF-1a and -2a). We have discovered that filamin A (FLNA), a large cytoskeletal actin-binding protein, physically interacts with HIF-1a and promotes tumor growth and angiogenesis. Hypoxia induces a calpain-dependent cleavage of FLNA to generate a naturally occurring C-terminal fragment that accumulates in the cell nucleus. This fragment interacts with the N-terminal portion of HIF-1a spanning amino acid residues 1-390 but not with HIF-2a. In hypoxia this fragment facilitates the nuclear localization of HIF-1a, is recruited to HIF-1a target gene promoters, and enhances HIF-1a function, resulting in up-regulation of HIF-1a target gene expression in a hypoxia-dependent fashion. These results unravel an important mechanism that selectively regulates the nuclear accumulation and function of HIF-1a and potentiates angiogenesis and tumor progression.
Source Title: Proceedings of the National Academy of Sciences of the United States of America
URI: http://scholarbank.nus.edu.sg/handle/10635/115763
ISSN: 00278424
DOI: 10.1073/pnas.1320815111/-/DCSupplemental
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