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High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

Authors
 Hanna Lee  ;  Minhee Park  ;  Nara Shin  ;  Gamin Kim  ;  Yun Gi Kim  ;  Jeon-Soo Shin  ;  Hoguen Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.424(2) : 321-326, 2012 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2012
MeSH
Active Transport, Cell Nucleus ; Colonic Neoplasms/metabolism* ; HCT116 Cells ; HMGB1 Protein/metabolism* ; Humans ; Nuclear Localization Signals/metabolism ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/genetics ; Protein Kinase C/metabolism* ; Serine/metabolism
Keywords
HMGB1 ; Phosphorylation ; Protein kinase C zeta ; Colorectal carcinoma
Abstract
High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X12012181
DOI
22750245
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gamin(김가민) ORCID logo https://orcid.org/0000-0001-8504-7921
Kim, Hogeun(김호근)
Park, Min Hee(박민희)
Shin, Na Ra(신나라)
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Lee, Hanna(이한나)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89704
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