Please use this identifier to cite or link to this item:
|Title:||Interplay of protein misfolding pathway and unfolded-protein response in acute promyelocytic leukemia||Authors:||Khan, M.||Keywords:||acute promyelocytic leukemia
nuclear receptor corepressor
promyelocytic leukemia retinoic acid receptor
|Issue Date:||Aug-2010||Citation:||Khan, M. (2010-08). Interplay of protein misfolding pathway and unfolded-protein response in acute promyelocytic leukemia. Expert Review of Proteomics 7 (4) : 591-600. ScholarBank@NUS Repository. https://doi.org/10.1586/epr.10.38||Abstract:||Protein misfolding has traditionally been linked to the pathogenesis of various neurodegenerative diseases. However, emerging evidence from various laboratories, including ours, suggests that protein misfolding may also play a fundamental role in some malignancies, particularly those caused by fusion oncoprotein generated from chromosomal translocation. Promyelocytic leukemia (PML) fused to the retinoic acid receptor (RAR) is a fusion oncoprotein linked to the transformation of acute promyelocytic leukemia (APL), and is not only a misfolded protein itself, but also promotes misfolding of nuclear receptor corepressor (N-CoR) protein, a corepressor essential for the growth-suppressive function of several tumor-suppressor proteins. PML-RAR promotes misfolding of N-CoR by inducing aberrant post-translational modification, which destabilizes its core and promotes instability. Misfolded N-CoR, thus, contributes to differentiation arrest and survival of APL cells through loss-of-function and aberrant gain-of-function properties. Therapeutic restoration of N-CoR conformation and function with conformation-modifying agents not only releases this differentiation arrest but also sensitizes APL cells to programmed cell death. These findings illustrate the potential of the misfolded N-CoR protein as a conformation-based drugable molecular target for APL, and highlights the promise of various conformation-modifying agents as novel therapeutics for APL. Protein conformational rearrangement, resulting from an inherited or acquired genetic alteration, could be a common pathological phenomenon contributing to transformation in different types of leukemias and solid tumors and, therefore, could serve as a common ground for designing a unifying diagnostic as well as therapeutic approach for a widely diverse disease such as cancer. To that end, APL could serve as a model for the development of a novel conformation-based therapeutic approach for other malignant diseases. © 2010 Expert Reviews Ltd.||Source Title:||Expert Review of Proteomics||URI:||http://scholarbank.nus.edu.sg/handle/10635/110817||ISSN:||14789450||DOI:||10.1586/epr.10.38|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jan 27, 2023
WEB OF SCIENCETM
checked on Jan 27, 2023
checked on Feb 2, 2023
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.