Ubiquitin C-terminal hydrolase37 regulates Tcf7 DNA binding for theactivation of Wnt signalling

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486624.do
DOI
10.1038/srep42590
Title
Ubiquitin C-terminal hydrolase37 regulates Tcf7 DNA binding for theactivation of Wnt signalling
Description
We thank Eek-hoon Jho (The University of Seoul) for providing ubiquitinplasmids. We also appreciate all members of our laboratory for helpfulcomments and supports. This work was supported by the National ResearchFoundation of Korea (NRF) grant funded by the Korea government (MSIP)(No. NRF-2014R1A2A2A01002859).
abstract
The Tcf/Lef family of transcription factors mediates the Wnt/beta-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling. Biochemical analyses demonstrated that deubiquitinating activity of Uch37 is not involved in Tcf7 protein stability but is required for the association of Tcf7 to target gene promoter in both Xenopus embryo and human liver cancer cells. In vivo analyses further revealed that Uch37 functions as a positive regulator of the Wnt/beta-catenin pathway downstream of beta-catenin stabilization that is required for the expression of ventrolateral mesoderm genes during Xenopus gastrulation. Our study provides a new mechanism for chromatin occupancy of Tcf7 and uncovers the physiological significance of Uch37 during early vertebrate development by regulating the Wnt/beta-catenin pathway.
provenance
Made available in Cube on 2018-09-28T16:12:35Z (GMT). No. of bitstreams: 0
language
English
author
Han, Wonhee
Lee, Hyeyoon
Han, Jin-Kwan
accessioned
2018-09-28T16:12:35Z
available
2018-09-28T16:12:35Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486624.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345273980
Jurisdiction
Rep.of Korea
Project Name
Program of Bio-Molecular Function
rights
openAccess
type
article


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