Cloning of a novel Apaf-1-interacting protein: a potent suppressor of apoptosis and ischemic neuronal cell death

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Guodong CaoJun Chen

Abstract

Cytochrome c-initiated activation of apoptotic protease activating factor-1 (Apaf-1) is a key step in the mitochondrial-signaling pathway for the activation of death-executing caspases in apoptosis. This signaling pathway has been implicated in the pathophysiology of various neurological disorders, including ischemic brain injury. In this study, we have cloned a novel rat gene product, designated as Apaf-1-interacting protein (AIP), which functions as a dominant-negative inhibitor of the Apaf-1-caspase-9 pathway. AIP is constitutively expressed in the brain, but at substantially lower levels than Apaf-1 and caspase-9. AIP can directly bind to Apaf-1 in vitro through its N-terminal caspase-recruiting domain, and this protein interaction was increased in cells undergoing apoptosis. Cytosolic extracts from cells overexpressing AIP were highly resistant to cytochrome c- dATP-induced activation of caspase-9 and caspase-3. Gene transfection of AIP into cell lines, including the neuronal-differentiated PC12 cells, potently suppressed apoptosis induced by various pro-apoptotic stimuli. To further investigate the functional role of AIP in primary neurons and in the brain, an adeno-associated virus (AAV) vector carrying the AIP cDNA was ...Continue Reading

Citations

Nov 4, 2011·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Joanna Iłżecka
Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jean F Soustiel, Sarit Larisch
Nov 14, 2013·PloS One·Thomas H SandersonMaik Hüttemann
Dec 5, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·R Anne StetlerJun Chen
Jun 8, 2012·Growth Factors·Emília P DuarteCarlos B Duarte
Oct 27, 2004·The Journal of Cell Biology·Dan Lindholm, Urmas Arumäe
Dec 30, 2014·Marine Drugs·Ai-Jiao XiaoHong-Shuo Sun
Apr 11, 2009·Journal of Neuroimmunology·V AndreoliA Quattrone
May 23, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·T S AbondanzaC Bincoletto
Jan 26, 2010·Medicinal Research Reviews·Enrique Pérez-PayáMaría J Vicent
Jun 8, 2006·Biochemical and Biophysical Research Communications·Wen-Wen ShengEr-Qing Wei
Oct 10, 2013·Ageing Research Reviews·David Yang-Wei FannThiruma V Arumugam
Dec 18, 2013·Mitochondrion·Neelu Yadav, Dhyan Chandra
May 9, 2006·Developmental Cell·Zachary T Schafer, Sally Kornbluth
Nov 5, 2016·Neurochemical Research·Yaobing YaoYanjie Jia
Feb 3, 2009·Stroke; a Journal of Cerebral Circulation·Brad R S BroughtonChristopher G Sobey
Sep 6, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nishad JayasundaraBarbara A Block
Jun 9, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anthony K F LiouJun Chen
Jul 25, 2017·Journal of Neuroinflammation·Biqiong ZhangWeizu Li
Jul 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alejandra Guerra-CastellanoIrene Díaz-Moreno
Mar 12, 2009·Cell Adhesion & Migration·Yan LiuDandan Sun
Mar 1, 2018·Physiological Reviews·Michael FrickerGuy C Brown
Jan 17, 2008·Journal of Medicinal Chemistry·L MondragónE Pérez-Payá
Aug 25, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Laura SkukanSrećko Gajović
Jun 2, 2009·Journal of Experimental & Clinical Cancer Research : CR·Shuhong ZhangChengyong Qin

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