Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress

Qadri, O and Bashir, S and Banday, M and Hilal, N and Majeed, Y and Fatima, NI and Pal, D and Fazili, KM (2024) Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress. In: Biochimica et Biophysica Acta - Molecular Cell Research, 1871 (7).

PDF Bio_Bio_Act_Mol_Cel_Res_1871_7Oct_2024_119774.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy

Abstract

The Endoplasmic Reticulum is a pervasive, dynamic cellular organelle that performs a wide range of functions in the eukaryotic cell, including protein folding and maturation. Upon stress, ER activates an adaptive cellular pathway, namely Unfolded Protein Response, that transduces information from ER to nucleus, restoring homeostasis in the ER milieu. UPR consists of three membrane-tethered sensors; IRE1, PERK and ATF6. Among all the UPR sensors, the IRE1 branch acts as a central pathway that orchestrates several pathways to determine cell fate. However, the detailed knowledge underlying the whole process is not understood yet. Previously, we determined the sMEK1 as one of the interacting partners of IRE1. sMEK1 is a protein phosphatase, which has been indicated in a number of critical cellular functions like apoptosis, cell proliferation, and tumour suppression. In this study, we evaluated the role of sMEK1 on the IRE1 signalling pathway. Our data indicate that sMEK1 can inhibit IRE1 phosphorylation under ER stress. This inhibitory effect of sMEK1 could be reflected in its downstream effectors, Xbp1 and RIDD, which are downregulated in the presence of sMEK1. We also found that the repressing effect of sMEK1 was specific to the IRE1 signalling pathway and could be preserved even under prolonged ER stress. Our findings also indicate that sMEK1 can inhibit IRE1 and its downstream molecules under ER stress irrespective of other UPR sensors. These results help to draw the mechanistic details giving insights into different molecular connections of UPR with other pathways. © 2024

Item Type:	Journal Article
Publication:	Biochimica et Biophysica Acta - Molecular Cell Research
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to Elsevier B.V.
Keywords:	phosphoprotein phosphatase; tumor suppressor protein, apoptosis; Article; cancer inhibition; cell function; cell organelle; cell proliferation; endoplasmic reticulum; endoplasmic reticulum stress; gene knockdown; genetic transfection; homeostasis; mammal cell; nonhuman; protein folding; signal transduction; unfolded protein response
Department/Centre:	Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited:	31 Jul 2024 05:10
Last Modified:	31 Jul 2024 05:10
URI:	http://eprints.iisc.ac.in/id/eprint/85690

Actions (login required)

View Item