A novel apoptotic pathway dependent on ribosome

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagasaki University
• Principal Investigator: HOTOKEZAKA Yuka NAGASAKI University, SCHOOL OF DENTISTRY, DEPARTMENT OF RADIOLOGY AND CANCER BIOLOGY, ASSISTANT PROFESSOR, 医学部・歯学部附属病院, 助手 (10244089)
• Co-Investigator(Kenkyū-buntansha): KATAYAMA Ikuo NAGASAKI University, SCHOOL OF DENTISTRY, DEPARTMENT OF RADIOLOGY AND CANCER BIOLOGY, INSTRUCTOR, 医学部・歯学部附属病院, 助手 (80295089) ; SUMI Tadateru NAGASAKI University, SCHOOL OF DENTISTRY, DEPARTMENT OF RADIOLOGY AND CANCER BIOLOGY, INSTRUCTOR, 大学院医歯薬学総合研究科, 助手 (80284701) ; TASHIRO Shigeki NAGASAKI University, SCHOOL OF DENTISTRY, DEPARTMENT OF RADIOLOGY AND CANCER BIOLOGY, INSTRUCTOR, 大学院医歯薬学総合研究科, 助手 (20300882) ; NAKAMURA Takashi NAGASAKI University, SCHOOL OF DENTISTRY, DEPARTMENT OF RADIOLOGY AND CANCER BIOLOGY, PROFESSOR, 大学院医歯薬学総合研究科, 教授 (30172406)
• Project Period (FY): 2005 – 2006
• Keywords: αNAC / apoptosis / ribosome / ER stress / siRNA

Research Abstract

It is now well recognized that there are two main pathway for the induction of apoptosis, the extrinsic or receptor-mediated pathway, and the intrinsic or mitochondria pathway. The intrinsic pathway is the most common pathway for cell death and can be activated by variety of stimuli. Theses stimuli cause the permeabilizaton of the mitochondria outer membrane and release of cytochrome c. Cytochrome c binds to the apoptosis protease-activationg factor (Apaf-1) and pro-casepase-9 molecules forming a caspase-activating complex, the apoptosome. The extrinsic pathway is activated by the interaction of a specific death ligand with its cell surface death receptors. We found that αNAC (nascent polypeptide-associated complex) is related with apoptosis. αNAC is known to play a role of binding of nascent chain emerging from ribosome and protecting them. We have an idea that there may be other pathway for the induction of apoptosis related with ribosome adding two main ones. Here we show that apoptosis is induced in cells by αNAC depletion using siRNA and the pathway of them may be related with ER (endoplasmic reticulum) stress.