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Biochim Biophys Acta. 2016 Sep;1863(9):2345-57. doi: 10.1016/j.bbamcr.2016.06.010. Epub 2016 Jun 29.

Terminal regions of β-catenin are critical for regulating its adhesion and transcription functions.

Author information

1
Academy of Scientific and Innovative Research (AcSIR), New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, J&K, India.
2
School of Life Sciences, Central University of Himachal Pradesh, Himachal Pradesh, India.
3
Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, USA.
4
Academy of Scientific and Innovative Research (AcSIR), New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, J&K, India. Electronic address: jamal@iiim.res.in.

Abstract

β-Catenin, the central molecule of canonical Wnt signaling pathway, has multiple binding partners and performs many roles in the cell. Apart from being a transcriptional activator, β-catenin acts as a crucial effector component of cadherin/catenin complex to physically interact with actin cytoskeleton along with α-catenin and E-cadherin for regulating cell-cell adhesion. Here, we have generated a library of β-catenin point and deletion mutants to delineate regions within β-catenin that are important for α-catenin-β-catenin interaction, nuclear localization, and transcriptional activity of β-catenin. We observed a unique mechanism for nuclear localization of β-catenin and its mutants and show that N-terminal exon-3 region and C-terminal domain of β-catenin are critical for this activity of β-catenin. Furthermore, we show HepG2 cells have high β-catenin mediated transcriptional activity due to the presence of an interstitial deletion at the N-terminal region of β-catenin. Due to this deletion mutant (hereupon called TM), GSK3β and HDAC inhibitors failed to show any impact whereas curcumin significantly inhibited β-catenin mediated transcriptional activity reiterating that TM is primarily responsible for the high transcriptional activity of HepG2 cells. Moreover, we show the recombinant TM does not physically interact with α-catenin, localizes predominantly in the nucleus, and has nearly two-fold higher transcriptional activity than the wildtype β-catenin.

KEYWORDS:

Beta-catenin signaling; Cancer; Cell proliferation and differentiation; Cellular signaling; HepG2 cells; Transcription factors

PMID:
27368802
DOI:
10.1016/j.bbamcr.2016.06.010
[Indexed for MEDLINE]
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