Raf-1 is a binding partner of DSCR1.
Down syndrome critical region 1 (DSCR1) is recognized as an endogenous calcineurin inhibitor. DSCR1 is induced in endothelial cells and may play an important role in inflammation and angiogenesis. To address a novel function of DSCR1, we searched interacting partners of DSCR1. We performed pull-down analysis using DSCR1 as a bait and identified Raf-1 as a binding partner. The association of Raf-1 was confirmed by co-immunoprecipitation in GM7373 cells expressing green fluorescence protein tagged DSCR1. We determined two Raf-1 binding regions in DSCR1; one in the N-terminus and the other in the C-terminus regions. We further demonstrated that calpain cleaved DSCR1 and generated fragments with different binding affinity to Raf-1 or calcineurin. These results constitute the first demonstration of Raf-1 as a binding partner of DSCR1, and suggest a novel role of DSCR1.
Cho
Young-Jin
YJ
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Abe
Mayumi
M
Kim
Seong Yun
SY
Sato
Yasufumi
Y
D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*
D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D019908:Proto-Oncogene Proteins c-raf; D019703:Calcineurin