title: p21-activated kinase 4 regulates HIF-1α translation in cancer cells.
abstract: The p21-activated kinases (Paks) interact with Rac/Cdc42 GTPases to regulate the actin cytoskeleton as well as various signaling pathways. Although activation of Paks in many human cancers is known to mediate cancer progression, the role of Pak proteins in hypoxia is poorly understood. In this study, we found that both Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-inducible factor-1α (HIF-1α) in hypoxia. We further discovered that Pak4 regulates HIF-1α translation via the Akt-mTOR-4E-BP1 pathway under hypoxic conditions. These results support a novel connection between HIF-1α and Pak4 in hypoxic cancer cells, and provide insights into mechanisms whereby tumors respond to and thrive under oxygen-deficient conditions.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, KIST Campus, University of Science and Technology (UST), Seoul 02792, Republic of Korea.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Woo
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biomedical Engineering, KIST Campus, University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address: soyeonkim@kist.re.kr.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, KIST Campus, University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address: eunyang@kist.re.kr.
authors.forename: Eun Gyeong
authors.initials: EG
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010750:Phosphoproteins; D008156:Luciferases; C546842:MTOR protein, human; C116367:PAK4 protein, human; C515903:PAK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D054462:p21-Activated Kinases
keywords: 4E-BP1; Akt; HIF-1α; Hypoxia; Pak4; mTOR