Heregulin promotes expression and subcellular redistribution of ADP-ribosylation factor 3.
To identify genes whose expression is modulated by heregulin-beta1 (HRG), a regulatory polypeptide for mammary epithelial cells, we performed differential display screening of MCF-7 cell mRNA. One cDNA clone upregulated by HRG was identical to human ADP-ribosylation factor 3 (ARF3), a guanine nucleotide-binding protein functioning in vesicular trafficking, phospholipase D activation and intracellular transport. HRG treatment increased expression of ARF3 mRNA and protein. Also, HRG triggered a rapid redistribution of ARF3, first to cell membranes and then to the nuclear compartment, where ARF3 colocalized with acetylated histone H3 in discrete regions. In addition, the ARF3 protein was developmentally regulated in the mammary gland with the highest levels in virgin and post-weaning glands. Together, these findings suggest for the first time that stimulation of ARF3 expression, subcellular redistribution and interaction with acetylated histone H3 may play a role in the action of HRG in mammary epithelial cells.
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Feng
F
Li
Mahitosh
M
Mandal
Sandip K
SK
Mishra
Christopher J
CJ
Barnes
Rakesh
R
Kumar
D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000107:Acetylation; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020890:Neuregulin-1 / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D006657:Histones; D020890:Neuregulin-1; C116687:ARF3 protein, human; D020727:ADP-Ribosylation Factors