Kim, Hyunju Na, Yu-Ran Kim, So Yeon Yang, Eun Gyeong 2024-01-20T04:34:36Z 2024-01-20T04:34:36Z 2021-09-05 2016-03 0730-2312 https://pubs.kist.re.kr/handle/201004/124327 Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is one of the key transcription factors that mediate adaptation to hypoxia. Despite increasing evidence implicating the PKC family as potential modulators of HIF-1 alpha, the molecular mechanisms of PKC isoform-dependent HIF-1 alpha activity under hypoxic conditions have not been systematically elucidated in cancer cell lines. Here, we collectively investigated how each isoform of the PKC family contributes to HIF-1 alpha accumulation in the human cervical cancer cell line HeLa. Among the abundant PKC isoforms, blockade of either PKC alpha or PKC delta was found to substantially reduce HIF-1 alpha accumulation and transcriptional activity in hypoxic cells. Knockdown of PKC delta resulted in a reduction of HIF-1 alpha mRNA levels, whereas the HIF-1 alpha mRNA level was unchanged regardless of PKC alpha knockdown. Upon searching for the downstream effectors of these kinases, we found that PKC alpha controls HIF-1 alpha translation via AKT-mTOR under hypoxic conditions. On the other hand, one of the well-known transcriptional regulation pathways of HIF-1 alpha, nuclear factor-kappa B (NF-kappa B) is identified as a downstream effector of PKC delta. Taken together, our findings provide insights into the roles of PKC isoforms as additional, discrete modulators of hypoxia-stimulated HIF-1 alpha accumulation through different signaling pathways. (C) 2015 Wiley Periodicals, Inc. English WILEY-BLACKWELL NF-KAPPA-B GENE-EXPRESSION PKC-DELTA ENDOTHELIAL-CELLS MAMMALIAN TARGET TUMOR-SUPPRESSOR HIF-ALPHA ACTIVATION HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA HIF-1-ALPHA Protein Kinase C Isoforms Differentially Regulate Hypoxia-Inducible Factor-1 alpha Accumulation in Cancer Cells Article 10.1002/jcb.25314 1 JOURNAL OF CELLULAR BIOCHEMISTRY, v.117, no.3, pp.647 - 658 JOURNAL OF CELLULAR BIOCHEMISTRY 117 3 647 658 scie scopus 000368857900010 2-s2.0-84955361326 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article NF-KAPPA-B GENE-EXPRESSION PKC-DELTA ENDOTHELIAL-CELLS MAMMALIAN TARGET TUMOR-SUPPRESSOR HIF-ALPHA ACTIVATION HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA HIF-1-ALPHA PKC alpha PKC delta HIF-1 alpha HYPOXIA mTOR NF-kappa B