Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.

Journal of Alzheimer's Disease : JAD
Jingtian ZhangXuemin Xu

Abstract

Presenilin-associated protein (PSAP) was originally identified as a mitochondrial proapoptotic protein. To further explore the apoptotic pathway that involves PSAP, our yeast two-hybrid screen revealed that PSAP interacts with a death receptor, DR6. DR6 is a relatively less common member of the death receptor family and has been shown to mediate the neurotoxicity of amyloid-β, mutant SOD1, and prion proteins and has also been implicated in the regulation of immune cell proliferation and differentiation. Our previous study showed that DR6 induces apoptosis via a unique mitochondria-dependent pathway different from the conventional death receptor-mediated extrinsic apoptotic pathways. Thus, the interaction of DR6 with PSAP established a direct molecular link between DR6 and mitochondrial apoptotic pathway. We investigated the possible role of PSAP in DR6-induced apoptosis. Interestingly, it was discovered that knockdown of PSAP strongly inhibited DR6-induced apoptosis. To further elucidate the mechanism by which PSAP mediates DR6-induced mitochondria-dependent apoptosis, our data demonstrated that knockdown of PSAP blocked DR6-induced Bax translocation and cytochrome c release from the mitochondria. Moreover, it was found that bo...Continue Reading

References

Oct 16, 2002·The Journal of Biological Chemistry·Xuemin XuMei-Zhen Cui
Jan 8, 2003·The Journal of Experimental Medicine·Clint S SchmidtSongqing Na
Oct 27, 2007·Cancer Immunology, Immunotherapy : CII·David C DeRosaRobert J Benschop
Feb 20, 2009·Nature·Anatoly NikolaevMarc Tessier-Lavigne
Jun 13, 2009·Cell Death and Differentiation·M OttS Orrenius
May 4, 2010·Nature Cell Biology·Yehudit ZaltsmanAtan Gross
Sep 27, 2012·BMB Reports·Eun-Woo LeeJaewhan Song
Mar 29, 2013·Journal of Bioenergetics and Biomembranes·Nancy P Gómez-CrisóstomoEduardo Martínez-Abundis
May 9, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dara Y KallopRobby M Weimer
Apr 23, 2015·Journal of Molecular Neuroscience : MN·Yunsheng WangLifeng Yang
Jan 4, 2017·Nature Communications·Daisuke FujikuraToshimitsu Uede
Mar 14, 2017·Current Biology : CB·Kanchana K GamageChristopher D Deppmann

❮ Previous
Next ❯

Methods Mentioned

BETA
two-hybrid
transfections
immunoprecipitation
co-immunoprecipitation
transfection

Software Mentioned

- SCAN - IT
UN
CLONTECH
GraphPad
PRISM
Gel Digitizing

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis