Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.

The ubiquitin-proteasome system plays important roles in various biological processes as it degrades the majority of cellular proteins. Adequate proteasomal degradation of crucial transcription regulators ensures the proper development of neutrophils. The ubiquitin E3 ligase of Growth factor indepen...

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Autores principales:	Shuo Gao, Zixuan Wang, Luxiang Wang, Haihong Wang, Hao Yuan, Xiaohui Liu, Saijuan Chen, Zhu Chen, Hugues de Thé, Wenqing Zhang, Yiyue Zhang, Jun Zhu, Jun Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/074e248f45494816a93de01799d651a8
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spelling	oai:doaj.org-article:074e248f45494816a93de01799d651a82021-12-02T20:03:24ZIrf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.1553-73901553-740410.1371/journal.pgen.1009693https://doaj.org/article/074e248f45494816a93de01799d651a82021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009693https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404The ubiquitin-proteasome system plays important roles in various biological processes as it degrades the majority of cellular proteins. Adequate proteasomal degradation of crucial transcription regulators ensures the proper development of neutrophils. The ubiquitin E3 ligase of Growth factor independent 1 (GFI1), a key transcription repressor governing terminal granulopoiesis, remains obscure. Here we report that the deficiency of the ring finger protein Interferon regulatory factor 2 binding protein 2a (Irf2bp2a) leads to an impairment of neutrophils differentiation in zebrafish. Mechanistically, Irf2bp2a functions as a ubiquitin E3 ligase targeting Gfi1aa for proteasomal degradation. Moreover, irf2bp2a gene is repressed by Gfi1aa, thus forming a negative feedback loop between Irf2bp2a and Gfi1aa during neutrophils maturation. Different levels of GFI1 may turn it into a tumor suppressor or an oncogene in malignant myelopoiesis. Therefore, discovery of certain drug targets GFI1 for proteasomal degradation by IRF2BP2 might be an effective anti-cancer strategy.Shuo GaoZixuan WangLuxiang WangHaihong WangHao YuanXiaohui LiuSaijuan ChenZhu ChenHugues de ThéWenqing ZhangYiyue ZhangJun ZhuJun ZhouPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009693 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Shuo Gao Zixuan Wang Luxiang Wang Haihong Wang Hao Yuan Xiaohui Liu Saijuan Chen Zhu Chen Hugues de Thé Wenqing Zhang Yiyue Zhang Jun Zhu Jun Zhou Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
description	The ubiquitin-proteasome system plays important roles in various biological processes as it degrades the majority of cellular proteins. Adequate proteasomal degradation of crucial transcription regulators ensures the proper development of neutrophils. The ubiquitin E3 ligase of Growth factor independent 1 (GFI1), a key transcription repressor governing terminal granulopoiesis, remains obscure. Here we report that the deficiency of the ring finger protein Interferon regulatory factor 2 binding protein 2a (Irf2bp2a) leads to an impairment of neutrophils differentiation in zebrafish. Mechanistically, Irf2bp2a functions as a ubiquitin E3 ligase targeting Gfi1aa for proteasomal degradation. Moreover, irf2bp2a gene is repressed by Gfi1aa, thus forming a negative feedback loop between Irf2bp2a and Gfi1aa during neutrophils maturation. Different levels of GFI1 may turn it into a tumor suppressor or an oncogene in malignant myelopoiesis. Therefore, discovery of certain drug targets GFI1 for proteasomal degradation by IRF2BP2 might be an effective anti-cancer strategy.
format	article
author	Shuo Gao Zixuan Wang Luxiang Wang Haihong Wang Hao Yuan Xiaohui Liu Saijuan Chen Zhu Chen Hugues de Thé Wenqing Zhang Yiyue Zhang Jun Zhu Jun Zhou
author_facet	Shuo Gao Zixuan Wang Luxiang Wang Haihong Wang Hao Yuan Xiaohui Liu Saijuan Chen Zhu Chen Hugues de Thé Wenqing Zhang Yiyue Zhang Jun Zhu Jun Zhou
author_sort	Shuo Gao
title	Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
title_short	Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
title_full	Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
title_fullStr	Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
title_full_unstemmed	Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.
title_sort	irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of gfi1aa in zebrafish.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/074e248f45494816a93de01799d651a8
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Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish.

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