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Title: Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ

Abstract

HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington's, Parkinson's diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies imply that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated thatmore » constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S).« less

Authors:
; ; ; ;  [1];  [2];  [1]
  1. Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL (United States)
  2. Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Science, Cleveland State University, Cleveland, OH (United States)
Publication Date:
OSTI Identifier:
22212265
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 318; Journal Issue: 10; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CELL CYCLE; CONCENTRATION RATIO; HEAT; HEAT-SHOCK PROTEINS; LIMBS; LYMPHOKINES; MAMMARY GLANDS; MELANOMAS; NERVOUS SYSTEM DISEASES; STEM CELLS

Citation Formats

Andrews, Joel F., Sykora, Landon J., Barik Letostak, Tiasha, Menezes, Mitchell E., Mitra, Aparna, Barik, Sailen, Shevde, Lalita A., and Samant, Rajeev S., E-mail: rsamant@usouthal.edu. Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ. United States: N. p., 2012. Web. doi:10.1016/J.YEXCR.2012.03.024.
Andrews, Joel F., Sykora, Landon J., Barik Letostak, Tiasha, Menezes, Mitchell E., Mitra, Aparna, Barik, Sailen, Shevde, Lalita A., & Samant, Rajeev S., E-mail: rsamant@usouthal.edu. Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ. United States. https://doi.org/10.1016/J.YEXCR.2012.03.024
Andrews, Joel F., Sykora, Landon J., Barik Letostak, Tiasha, Menezes, Mitchell E., Mitra, Aparna, Barik, Sailen, Shevde, Lalita A., and Samant, Rajeev S., E-mail: rsamant@usouthal.edu. 2012. "Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ". United States. https://doi.org/10.1016/J.YEXCR.2012.03.024.
@article{osti_22212265,
title = {Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ},
author = {Andrews, Joel F. and Sykora, Landon J. and Barik Letostak, Tiasha and Menezes, Mitchell E. and Mitra, Aparna and Barik, Sailen and Shevde, Lalita A. and Samant, Rajeev S., E-mail: rsamant@usouthal.edu},
abstractNote = {HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington's, Parkinson's diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies imply that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated that constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S).},
doi = {10.1016/J.YEXCR.2012.03.024},
url = {https://www.osti.gov/biblio/22212265}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 10,
volume = 318,
place = {United States},
year = {Sun Jun 10 00:00:00 EDT 2012},
month = {Sun Jun 10 00:00:00 EDT 2012}
}