ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6

RNA binding proteins (RBPs)-mediated post-transcriptional control has been implicated in influencing various aspects of RNA metabolism and playing important roles in mammalian development and pathological diseases. However, the functions of specific RBPs and the molecular mechanisms through which th...

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Main Authors:	Chen, Ming-Tai, Dong, Lei, Zhang, Xin-Hua, Yin, Xiao-Lin, Ning, Hong-Mei, Shen, Chao, Su, Rui, Li, Feng, Song, Li, Ma, Yan-Ni, Wang, Fang, Zhao, Hua-Lu, Yu, Jia, Zhang, Jun-Wu
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635361/

id	pubmed-4635361
recordtype	oai_dc
spelling	pubmed-46353612015-11-25 ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6 Chen, Ming-Tai Dong, Lei Zhang, Xin-Hua Yin, Xiao-Lin Ning, Hong-Mei Shen, Chao Su, Rui Li, Feng Song, Li Ma, Yan-Ni Wang, Fang Zhao, Hua-Lu Yu, Jia Zhang, Jun-Wu Article RNA binding proteins (RBPs)-mediated post-transcriptional control has been implicated in influencing various aspects of RNA metabolism and playing important roles in mammalian development and pathological diseases. However, the functions of specific RBPs and the molecular mechanisms through which they act in monocyte/macrophage differentiation remain to be determined. In this study, through bioinformatics analysis and experimental validation, we identify that ZFP36L1, a member of ZFP36 zinc finger protein family, exhibits significant decrease in acute myeloid leukemia (AML) patients compared with normal controls and remarkable time-course increase during monocyte/macrophage differentiation of PMA-induced THP-1 and HL-60 cells as well as induction culture of CD34+ hematopoietic stem/progenitor cells (HSPCs). Lentivirus-mediated gain and loss of function assays demonstrate that ZFP36L1 acts as a positive regulator to participate in monocyte/macrophage differentiation. Mechanistic investigation further reveals that ZFP36L1 binds to the CDK6 mRNA 3′untranslated region bearing adenine-uridine rich elements and negatively regulates the expression of CDK6 which is subsequently demonstrated to impede the in vitro monocyte/macrophage differentiation of CD34+ HSPCs. Collectively, our work unravels a ZFP36L1-mediated regulatory circuit through repressing CDK6 expression during monocyte/macrophage differentiation, which may also provide a therapeutic target for AML therapy. Nature Publishing Group 2015-11-06 /pmc/articles/PMC4635361/ /pubmed/26542173 http://dx.doi.org/10.1038/srep16229 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Ming-Tai Dong, Lei Zhang, Xin-Hua Yin, Xiao-Lin Ning, Hong-Mei Shen, Chao Su, Rui Li, Feng Song, Li Ma, Yan-Ni Wang, Fang Zhao, Hua-Lu Yu, Jia Zhang, Jun-Wu
spellingShingle	Chen, Ming-Tai Dong, Lei Zhang, Xin-Hua Yin, Xiao-Lin Ning, Hong-Mei Shen, Chao Su, Rui Li, Feng Song, Li Ma, Yan-Ni Wang, Fang Zhao, Hua-Lu Yu, Jia Zhang, Jun-Wu ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
author_facet	Chen, Ming-Tai Dong, Lei Zhang, Xin-Hua Yin, Xiao-Lin Ning, Hong-Mei Shen, Chao Su, Rui Li, Feng Song, Li Ma, Yan-Ni Wang, Fang Zhao, Hua-Lu Yu, Jia Zhang, Jun-Wu
author_sort	Chen, Ming-Tai
title	ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
title_short	ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
title_full	ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
title_fullStr	ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
title_full_unstemmed	ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
title_sort	zfp36l1 promotes monocyte/macrophage differentiation by repressing cdk6
description	RNA binding proteins (RBPs)-mediated post-transcriptional control has been implicated in influencing various aspects of RNA metabolism and playing important roles in mammalian development and pathological diseases. However, the functions of specific RBPs and the molecular mechanisms through which they act in monocyte/macrophage differentiation remain to be determined. In this study, through bioinformatics analysis and experimental validation, we identify that ZFP36L1, a member of ZFP36 zinc finger protein family, exhibits significant decrease in acute myeloid leukemia (AML) patients compared with normal controls and remarkable time-course increase during monocyte/macrophage differentiation of PMA-induced THP-1 and HL-60 cells as well as induction culture of CD34+ hematopoietic stem/progenitor cells (HSPCs). Lentivirus-mediated gain and loss of function assays demonstrate that ZFP36L1 acts as a positive regulator to participate in monocyte/macrophage differentiation. Mechanistic investigation further reveals that ZFP36L1 binds to the CDK6 mRNA 3′untranslated region bearing adenine-uridine rich elements and negatively regulates the expression of CDK6 which is subsequently demonstrated to impede the in vitro monocyte/macrophage differentiation of CD34+ HSPCs. Collectively, our work unravels a ZFP36L1-mediated regulatory circuit through repressing CDK6 expression during monocyte/macrophage differentiation, which may also provide a therapeutic target for AML therapy.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635361/
_version_	1613498240715456512

ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6

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