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Kr-POK (ZBTB7c) regulates cancer cell proliferation through glutamine metabolism

Authors
 Man-Wook Hur  ;  Jae-Hyeon Yoon  ;  Min-Young Kim  ;  Hyeonseok Ko  ;  Bu-Nam Jeon 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, Vol.1860(8) : 829-838, 2017 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 
ISSN
 1874-9399 
Issue Date
2017
MeSH
Animals ; Cell Death/genetics ; Cell Line ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics ; Glutaminase/metabolism ; Glutamine/metabolism* ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms/genetics ; Neoplasms/metabolism ; Proteins/metabolism* ; RNA, Small Interfering/genetics ; STAT1 Transcription Factor/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/genetics
Keywords
GLS1 ; Glutamine metabolism ; Kr-POK (Zbtb7c) ; PIAS1 ; p-STAT1
Abstract
Kr-POK (ZBTB7c) is a kidney cancer-related POK transcription factor that not only represses transcription of CDKN1A but also increases expression of FASN. However, precisely how Kr-POK affects cell metabolism by controlling gene expression in response to an energy source in rapidly proliferating cells remains unknown. In this study, we characterized the molecular and functional features of Kr-POK in the context of tumor growth and glutamine metabolism. We found that cells expressing Kr-POK shRNA exhibited more severe cell death than control cells in glucose-deprived medium, and that knockdown of Kr-POK decreased glutamine uptake. Glutamine is critical for tumor cell proliferation. Glutaminase (GLS1), which is activated by p-STAT1, catalyzes the initial reaction in the pathway of glutaminolysis. Kr-POK interacts with PIAS1 to disrupt the interaction between PIAS1 and p-STAT1, and free p-STAT1 can activate GLS1 transcription through an interaction with p300. Kr-POK can be also sumoylated by PIAS1, facilitating Kr-POK degradation by the ubiquitin-mediated proteasomal pathway. Finally, we showed that repression of Kr-POK inhibited tumor growth in vivo in a xenograft model by repressing GLS1 expression. Taken together, our data reveal that Kr-POK activates GLS1 transcription and increases glutamine uptake to support rapid cancer cell proliferation.
Full Text
https://www.sciencedirect.com/science/article/pii/S187493991730038X
DOI
10.1016/j.bbagrm.2017.05.005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Jeon, Bu Nam(전부남)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160601
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