Regulation of polyamine homeostasis through an antizyme citrullination pathway

doi:10.1002/jcp.30252

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23637

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23637

Title:	Regulation of polyamine homeostasis through an antizyme citrullination pathway
Authors:	Yang, YF;Lee, CY;Hsieh, JY;Liu, YL;Lin, CL;Liu, GY;Hung, HC
Keywords:	anti-citrullinated AZ antibody;antizyme;ornithine decarboxylase;peptidylarginine deiminase;polyamines;protein citrullination
Date:	2021
Issue Date:	2022-08-05T09:40:29Z (UTC)
Publisher:	WILEY
ISSN:	0021-9541
Abstract:	This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4-overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C-terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4-mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology.
URI:	http://dx.doi.org/10.1002/jcp.30252 https://www.webofscience.com/wos/woscc/full-record/WOS:000606789500001 https://ir.csmu.edu.tw:8080/handle/310902500/23637
Relation:	JOURNAL OF CELLULAR PHYSIOLOGY ,2021,v236,issue 8, P5646-5663
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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