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FASEB J. 2019 May;33(5):6574-6583. doi: 10.1096/fj.201801937RR. Epub 2019 Feb 26.

Subcellular localization of mutated β-catenins with different incidences of cis-peptide bonds at the Xaa246-P247 site in HepG2 cells.

Author information

1
School of Life Sciences, Chongqing University, Chongqing, China.
2
Information Institute of Southwest University, Southwest University, Chongqing, China.
3
School of Life Science, Southwest University, Chongqing, China.
4
Department of Hematology, First Affiliated Hospital of Army Military Medical University, Chongqing, China.

Abstract

Mutations may ultimately change the local conformation of proteins; however, little attention has been paid to alterations in protein function caused by the incidence of cis-peptide bonds (ICPB) in mammalian cells. In this study, a statistical approach, coimmunoprecipitation, and immunofluorescence staining have been used to confirm that S246→Y and S246→W missense mutations, which help increase the ICPB in Xaa246-P247 (Xaa is any amino acid) in human β-catenin, can reduce the interactions between β-catenin and adenomatous polyposis coli (APC) and between β-catenin and Ca2+-dependent cell adhesion molecule family in epithelial tissue (E-cadherin), eventually leading to increased nuclear migration of β-catenin in the HepG2 cell line (an immortalized cell line consisting of human liver carcinoma cells). Conversely, S246→L and S246→M missense mutations, which reduce the ICPB in Xaa246-P247 in human β-catenin, can enhance interactions between β-catenin and APC and between β-catenin and E-cadherin, leading to decreased nuclear migration of β-catenin. These results not only indicate that a change in the ICPB may be an important cause of functional protein changes but also provide a new basis for the study of genetic disease prediction, gene diagnosis, individualized treatment, and protein modification at the gene level for clinicians and other professionals.-Yu, S., Zhang, Y., Wu, Y., Yang, H., Chen, Y., Yang, Y., Zhang, Z. Subcellular localization of mutated β-catenins with different incidences of cis-peptide bonds at the Xaa246-P247 site in HepG2 cells.

KEYWORDS:

APC; E-cadherin; ICPB; interaction; missense mutations

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