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A novel HIF1AN substrate KANK3 plays a tumor-suppressive role in hepatocellular carcinoma

Authors
 Iljin Kim  ;  Jengmin Kang  ;  Heon Yung Gee  ;  Jong-Wan Park 
Citation
 CELL BIOLOGY INTERNATIONAL, Vol.42(3) : 303-312, 2018 
Journal Title
 CELL BIOLOGY INTERNATIONAL 
ISSN
 1065-6995 
Issue Date
2018
Keywords
HIF1AN ; KANK3 ; hepatocellular carcinoma ; hydroxylation ; hypoxia
Abstract
The KN motif and ankyrin repeat domain-containing protein (KANK) family is involved in actin cytoskeleton organization and cell motility. Compared with other KANK members, the biological function of KANK3 is not clear. Here, we identified KANK3 as a new substrate for the oxygen sensor hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), which hydroxylates HIF-1/2alpha and other ankyrin repeat domain-containing proteins at asparagine residues. An in vitro hydroxylation assay clearly demonstrated asparaginyl hydroxylation of KANK3 by HIF1AN, and mass spectroscopic analysis revealed that KANK3 is hydroxylated at three asparagine residues within the ankyrin repeat domain. Bioinformatics analysis revealed that KANK3 downregulation is correlated with a poor prognosis in several types of cancers, including hepatocellular carcinoma (HCC). In HCC cells, KANK3 knockdown enhanced cell migration and invasion, while its overexpression inhibited these cell behaviors. Interestingly, such effects of KANK3 were not observed under hypoxic conditions, suggesting oxygen-dependent activity of KANK3. Based on these data, we propose that KANK3 acts as a tumor suppressor to control cancer behavior in an oxygen-dependent manner.
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1002/cbin.10895
DOI
10.1002/cbin.10895
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162053
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