Heregulin-induced apoptosis.
Heregulins (HRGs) are a group of polypeptide factors that are encoded by four different HRG genes that can express multiple isoforms through alternate RNA splicing. A number of HRG isoforms possess both growth stimulatory and growth inhibitory functions that are necessary for their important role in the development and maintenance of the heart, nervous system and epithelial cells in multiple organs including the breast. Growth inhibition by HRG relates to its ability to induce apoptosis, differentiation, and cell cycle G(2) arrest. Current studies suggest that HRGs can induce a unique form of apoptosis. In this article, we review recent progress in characterizing and understanding HRG-induced apoptosis. Particular attention has been given to: (1). the activation of caspases-7 and -9; (2). the role of the anti-apoptotic Bcl-2 protein; and (3). the signaling molecules and pathways that regulate HRG-induced apoptosis, including the p38, JNK, mTOR kinase, and PKC alpha kinase.
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Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Varela
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D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D020890:Neuregulin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases