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


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Article Info

DATE

2017-08-04

AUTHORS

Kazumi Take, Hironori Waki, Wei Sun, Takahito Wada, Jing Yu, Masahiro Nakamura, Tomohisa Aoyama, Toshimasa Yamauchi, Takashi Kadowaki

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. More... »

PAGES

7326

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-06469-5

DOI

http://dx.doi.org/10.1038/s41598-017-06469-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090989122

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28779110


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74 novel negative regulator
75 nucleus
76 obesity
77 overexpression
78 pancreatic β-cells
79 pathway
80 proinsulin
81 protein 1
82 protein levels
83 regulator
84 residues
85 results
86 role
87 role of CDKAL1
88 signaling pathways
89 stable overexpression
90 study
91 susceptibility genes
92 target gene expression
93 tissue
94 translation
95 type 2 diabetes
96 unphosphorylated form
97 β-catenin
98 β-catenin pathway
99 β-cells
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