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

Icli B, Bharti A, Pentassuglia L, Peng X, Sawyer DB
Biochem Biophys Res Commun. 2012 418 (1): 116-21

PMID: 22244893 · PMCID: PMC3273580 · DOI:10.1016/j.bbrc.2011.12.144

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 γ-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.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Animals Cell Nucleus Cyclin-Dependent Kinase Inhibitor p21 DNA Damage Doxorubicin ErbB Receptors Heart Ventricles Mice Myocytes, Cardiac Protein Kinase Inhibitors Quinazolines Rats Receptor, ErbB-4 Tumor Suppressor Protein p53 Tyrphostins

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