title: Grb7 and Hax1 may colocalize partially to mitochondria in EGF-treated SKBR3 cells and their interaction can affect Caspase3 cleavage of Hax1.
abstract: Growth factor receptor bound protein 7 (Grb7) is a signal-transducing adaptor protein that mediates specific protein-protein interactions in multiple signaling pathways. Grb7, with Grb10 and Grb14, is members of the Grb7 protein family. The topology of the Grb7 family members contains several protein-binding domains that facilitate the formation of protein complexes, and high signal transduction efficiency. Grb7 has been found overexpressed in several types of cancers and cancer cell lines and is presumed involved in cancer progression through promotion of cell proliferation and migration via interactions with the erythroblastosis oncogene B 2 (human epidermal growth factor receptor 2) receptor, focal adhesion kinase, Ras-GTPases, and other signaling partners. We previously reported Grb7 binds to Hax1 (HS1 associated protein X1) isoform 1, an anti-apoptotic protein also involved in cell proliferation and calcium homeostasis. In this study, we confirm that the in vitro Grb7/Hax1 interaction is exclusive to these two proteins and their interaction does not depend on Grb7 dimerization state. In addition, we report Grb7 and Hax1 isoform 1 may colocalize partially to mitochondria in epidermal growth factor-treated SKBR3 cells and growth conditions can affect this colocalization. Moreover, Grb7 can affect Caspase3 cleavage of Hax1 isoform 1 in vitro, and Grb7 expression may slow Caspase3 cleavage of Hax1 isoform 1 in apoptotic HeLa cells. Finally, Grb7 is shown to increase cell viability in apoptotic HeLa cells in a time-dependent manner. Taken together, these discoveries provide clues for the role of a Grb7/Hax1 protein interaction in apoptosis pathways involving Hax1. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA.
authors: Lei
authors: L
authors: Qian
authors: Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA.
authors: Andrew M
authors: AM
authors: Bradford
authors: Core University Research Resources Laboratory, New Mexico State University, Las Cruces, NM, 88003, USA.
authors: Peter H
authors: PH
authors: Cooke
authors: Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA.
authors: Barbara A
authors: BA
authors: Lyons
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051382:GRB7 Adaptor Protein / Q000378:metabolism*; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495955:GRB7 protein, human; C104759:HAX1 protein, human; D051382:GRB7 Adaptor Protein; D004815:Epidermal Growth Factor; C505407:CASP3 protein, human; D053148:Caspase 3; D002118:Calcium
keywords: Caspase3; Grb7; Hax1; SKBR3 cells; apoptosis; mitochondria; signal-transducing adaptor protein