Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0025268
Title: Role of chaperone mediated autophagy (CMA) in the degradation of misfolded N-CoR protein in non-small cell lung cancer (NSCLC) cells
Authors: Ali, A.B. 
Nin, D.S. 
Tam, J.
Khan, M. 
Issue Date: 23-Sep-2011
Citation: Ali, A.B., Nin, D.S., Tam, J., Khan, M. (2011-09-23). Role of chaperone mediated autophagy (CMA) in the degradation of misfolded N-CoR protein in non-small cell lung cancer (NSCLC) cells. PLoS ONE 6 (9) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0025268
Abstract: Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells. © 2011 Ali et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/110779
ISSN: 19326203
DOI: 10.1371/journal.pone.0025268
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2011-role_of_chaperone_mediated_autophagy-published.PDF599.56 kBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

20
checked on Jul 17, 2019

WEB OF SCIENCETM
Citations

2
checked on Jul 17, 2019

Page view(s)

70
checked on Jul 19, 2019

Download(s)

7
checked on Jul 19, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.