hTERT, the catalytic component of the human telomerase enzyme, is regulated by post-translational modifications, like phosphorylation and ubiquitination by multiple proteins which remarkably affects the overall activity of the enzyme. Here we report that hTERT gets SUMOylated by SUMO1 and polycomb protein CBX4 acts as the SUMO E3 ligase of hTERT. hTERT SUMOylation positively regulates its telomerase activity which can be inhibited by SENP3-mediated deSUMOylation. Interestingly, we have established a new role of hTERT SUMOylation in the repression of E-cadherin gene expression and consequent triggering on the epithelial-mesenchymal-transition (EMT) program in breast cancer cells. We also observed that catalytically active CBX4, leads to retention of hTERT/ZEB1 complex onto E-cadherin promoter leading to its repression through hTERT-SUMOylation. Further through wound healing and invasion assays in breast cancer cells, we showed the tumor promoting ability of hTERT was significantly compromised upon overexpression of SUMO-defective mutant of hTERT. Thus our findings establish a new post-translational modification of hTERT which on one hand is involved in telomerase activity maintenance and on the other hand plays a crucial role in the regulation of gene expression thereby promoting migration and invasion of breast cancer cells.
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October 2020
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Cover Image
The cover image showing the crystal structure of human hemoglobin (PDB: 1GZX). For more information, see the article by Natarajan et al. (pp. 3839–3850). Artwork Image courtesy of C. Natarajan.
Research Article|
October 12 2020
SUMO E3 ligase CBX4 regulates hTERT-mediated transcription of CDH1 and promotes breast cancer cell migration and invasion
Sulagna Sanyal;
Sulagna Sanyal
1Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, 92 A.P.C. Road, Kolkata 700009, India
2Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
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Payel Mondal;
Payel Mondal
2Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
3Homi Bhaba National Institute, Mumbai, India
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Sabyasachi Sen;
Sabyasachi Sen
2Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
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Sumita Sengupta (Bandyopadhyay);
Sumita Sengupta (Bandyopadhyay)
1Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, 92 A.P.C. Road, Kolkata 700009, India
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Chandrima Das
2Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
3Homi Bhaba National Institute, Mumbai, India
Correspondence: Chandrima Das (chandrima.das@saha.ac.in)
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Publisher: Portland Press Ltd
Received:
May 07 2020
Revision Received:
September 02 2020
Accepted:
September 14 2020
Accepted Manuscript online:
September 16 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (19): 3803–3818.
Article history
Received:
May 07 2020
Revision Received:
September 02 2020
Accepted:
September 14 2020
Accepted Manuscript online:
September 16 2020
Citation
Sulagna Sanyal, Payel Mondal, Sabyasachi Sen, Sumita Sengupta (Bandyopadhyay), Chandrima Das; SUMO E3 ligase CBX4 regulates hTERT-mediated transcription of CDH1 and promotes breast cancer cell migration and invasion. Biochem J 16 October 2020; 477 (19): 3803–3818. doi: https://doi.org/10.1042/BCJ20200359
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