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Title: ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

Abstract

Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiacmore » myocytes.« less

Authors:
 [1];  [2]; ;  [3]
  1. Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (United States)
  2. Center of Molecular Stress Response Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, MA 02118 (United States)
  3. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States)
Publication Date:
OSTI Identifier:
22207684
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 418; Journal Issue: 1; 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 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL STRESS; DNA DAMAGES; DOXORUBICIN; GENE REGULATION; INHIBITION; RATS; RECEPTORS; RNA; TYROSINE

Citation Formats

Icli, Basak, Bharti, Ajit, Pentassuglia, Laura, Peng, Xuyang, and Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2011.12.144.
Icli, Basak, Bharti, Ajit, Pentassuglia, Laura, Peng, Xuyang, & Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response. United States. https://doi.org/10.1016/J.BBRC.2011.12.144
Icli, Basak, Bharti, Ajit, Pentassuglia, Laura, Peng, Xuyang, and Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu. 2012. "ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response". United States. https://doi.org/10.1016/J.BBRC.2011.12.144.
@article{osti_22207684,
title = {ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response},
author = {Icli, Basak and Bharti, Ajit and Pentassuglia, Laura and Peng, Xuyang and Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu},
abstractNote = {Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.},
doi = {10.1016/J.BBRC.2011.12.144},
url = {https://www.osti.gov/biblio/22207684}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 418,
place = {United States},
year = {Fri Feb 03 00:00:00 EST 2012},
month = {Fri Feb 03 00:00:00 EST 2012}
}