CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway

Abstract CDK5 Regulatory Subunit-Associated Protein 1-like 1 (CDKAL1) was identified as a susceptibility gene for type 2 diabetes and body mass index in genome-wide association studies. Although it was reported that CDKAL1 is a methylthiotransferase essential for tRNALys(UUU) and faithful translatio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kazumi Take, Hironori Waki, Wei Sun, Takahito Wada, Jing Yu, Masahiro Nakamura, Tomohisa Aoyama, Toshimasa Yamauchi, Takashi Kadowaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a195ba72725844e2a8bc399e136fbc53
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a195ba72725844e2a8bc399e136fbc53
record_format	dspace
spelling	oai:doaj.org-article:a195ba72725844e2a8bc399e136fbc532021-12-02T16:06:40ZCDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway10.1038/s41598-017-06469-52045-2322https://doaj.org/article/a195ba72725844e2a8bc399e136fbc532017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06469-5https://doaj.org/toc/2045-2322Abstract CDK5 Regulatory Subunit-Associated Protein 1-like 1 (CDKAL1) was identified as a susceptibility gene for type 2 diabetes and body mass index in genome-wide association studies. Although it was reported that CDKAL1 is a methylthiotransferase essential for tRNALys(UUU) and faithful translation of proinsulin generated in pancreatic β cells, the role of CDKAL1 in adipocytes has not been understood well. In this study, we found that CDKAL1 is expressed in adipose tissue and its expression is increased during differentiation. Stable overexpression of CDKAL1, however, inhibited adipocyte differentiation of 3T3-L1 cells, whereas knockdown of CDKAL1 promoted differentiation. CDKAL1 increased protein levels of β-catenin and its active unphosphorylated form in the nucleus, thereby promoting Wnt target gene expression, suggesting that CDKAL1 activated the Wnt/β-catenin pathway—a well-characterized inhibitory regulator of adipocyte differentiation. Mutant experiments show that conserved cysteine residues of Fe-S clusters of CDKAL1 are essential for its anti-adipogenic action. Our results identify CDKAL1 as novel negative regulator of adipocyte differentiation and provide insights into the link between CDKAL1 and metabolic diseases such as type 2 diabetes and obesity.Kazumi TakeHironori WakiWei SunTakahito WadaJing YuMasahiro NakamuraTomohisa AoyamaToshimasa YamauchiTakashi KadowakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazumi Take Hironori Waki Wei Sun Takahito Wada Jing Yu Masahiro Nakamura Tomohisa Aoyama Toshimasa Yamauchi Takashi Kadowaki CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
description	Abstract CDK5 Regulatory Subunit-Associated Protein 1-like 1 (CDKAL1) was identified as a susceptibility gene for type 2 diabetes and body mass index in genome-wide association studies. Although it was reported that CDKAL1 is a methylthiotransferase essential for tRNALys(UUU) and faithful translation of proinsulin generated in pancreatic β cells, the role of CDKAL1 in adipocytes has not been understood well. In this study, we found that CDKAL1 is expressed in adipose tissue and its expression is increased during differentiation. Stable overexpression of CDKAL1, however, inhibited adipocyte differentiation of 3T3-L1 cells, whereas knockdown of CDKAL1 promoted differentiation. CDKAL1 increased protein levels of β-catenin and its active unphosphorylated form in the nucleus, thereby promoting Wnt target gene expression, suggesting that CDKAL1 activated the Wnt/β-catenin pathway—a well-characterized inhibitory regulator of adipocyte differentiation. Mutant experiments show that conserved cysteine residues of Fe-S clusters of CDKAL1 are essential for its anti-adipogenic action. Our results identify CDKAL1 as novel negative regulator of adipocyte differentiation and provide insights into the link between CDKAL1 and metabolic diseases such as type 2 diabetes and obesity.
format	article
author	Kazumi Take Hironori Waki Wei Sun Takahito Wada Jing Yu Masahiro Nakamura Tomohisa Aoyama Toshimasa Yamauchi Takashi Kadowaki
author_facet	Kazumi Take Hironori Waki Wei Sun Takahito Wada Jing Yu Masahiro Nakamura Tomohisa Aoyama Toshimasa Yamauchi Takashi Kadowaki
author_sort	Kazumi Take
title	CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
title_short	CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
title_full	CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
title_fullStr	CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
title_full_unstemmed	CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway
title_sort	cdk5 regulatory subunit-associated protein 1-like 1 negatively regulates adipocyte differentiation through activation of wnt signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a195ba72725844e2a8bc399e136fbc53
work_keys_str_mv	AT kazumitake cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT hironoriwaki cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT weisun cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT takahitowada cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT jingyu cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT masahironakamura cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT tomohisaaoyama cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT toshimasayamauchi cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway AT takashikadowaki cdk5regulatorysubunitassociatedprotein1like1negativelyregulatesadipocytedifferentiationthroughactivationofwntsignalingpathway
_version_	1718384920702746624

CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway

Ejemplares similares