Journal of Cell Science & Therapy
Open Access

TCR signaling via ZAP- 70 induced by CD3 stimulation is more active under acidic conditions

International Conference & Exhibition on Cell Science & Stem Cell Research

29 Nov - 1 Dec 2011 Philadelphia Airport Marriott, USA

Hiroshi Kobayashi

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

Mammalian int6 gene has been implicated in breast cancer formation; but its molecular functions remain unclear. We previously characterized yin6 , the fi ssion yeast homolog of int6, and demonstrated that it binds and regulates proper localization and/or assembly of 26S proteasomes. Th ese data support the hypothesis that Yin6 regulates proteasome, abnormalities in which can disrupt homeostasis of regulatory proteins leading to tumor formation. Th e goal of this study is to investigate the mechanisms. From a genetic screen, we established that overexpression of two proteins, Rpn7 and Arc3, rescued proteasome defects in yin6 -null cells. Rpn7 is a proteasome subunit that contains a PCI domain, also found in Int6/Yin6. We identifi ed a conserved Leu/Met residue in the PCI domain. Bioinformatics predicted that the hydrophobicity of this residue is critical for arrangement of �±-helical repeats within the PCI domain. Consistently, replacing it with Asp in Rpn7 and Yin6 inactivated these proteins and blocked their binding to other proteins. Arc3 is a subunit of the Arp2/3 complex, whose major role is to nucleate F-actin and regulate intracellular traffi cking. We found that proteasome mobility, and nuclear import in particular, were reduced when Arc3 was inactivated, leading to proteasome defects in the nucleus. To further explore proteasome nuclear transport, I investigated how Yin6 interacted with importins. Our genetics and mass-spectrometry data suggested that Yin6 selectively interacted with Sal3 to regulate proteasome nuclear import. In conclusion, our studies provided mechanistic insight into the role of Yin6 in ensuring proper proteasome assembly and mobility to infl uence many cellular processes

Biography :

Zhe Sha got his Ph.D degree from Baylor College of Medicine under the supervision of Professor Eric C. Chang. The work presented here was completed during his Ph.D research, during which he published 3 papers in reputed journals