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Caspase-3

Definition:

Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins. At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress. Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction. Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface.

References:

[1]. Tanusree Sen, et al. OGDHL is a modifier of AKT-dependent signaling and NF-κB function. PLoS One. 2012;7(11):e48770. [Content Brief]

[2]. Jun Suzuki, et al. Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science. 2013 Jul 26;341(6144):403-6. [Content Brief]

[3]. Jorge R Cabrera, et al. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem. 2011 Apr 22;286(16):14628-38. [Content Brief]

[4]. John G Walsh, et al. Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12815-9. [Content Brief]

[5]. D W Nicholson, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. [Content Brief]

[6]. Ting Peng, et al. Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases. Mol Cell. 2022 May 19;82(10):1806-1820.e8. [Content Brief]

[7]. Yaxin Liu, et al. Calmodulin Binding Activates Chromobacterium CopC Effector to ADP-Riboxanate Host Apoptotic Caspases. mBio. 2022 Jun 28;13(3):e0069022. [Content Brief]

[8]. Xiaohan Ning, et al. Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3. Mol Cell. 2019 Apr 4;74(1):19-31.e7. [Content Brief]

[9]. Nathan D Thomsen, et al. Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8477-82. [Content Brief]

[10]. Y P Goldberg, et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442-9. [Content Brief]

[11]. M Germain, et al. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J Biol Chem. 1999 Oct 1;274(40):28379-84. [Content Brief]

[12]. Hirokazu Nakatsumi, et al. Identification of functional regions defining different activity in caspase-3 and caspase-7 within cells. J Biol Chem. 2010 Aug 13;285(33):25418-25. [Content Brief]

[13]. Masahiro Maruoka, et al. Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane. Mol Cell. 2021 Apr 1;81(7):1397-1410.e9. [Content Brief]

[14]. M Tewari, et al. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801-9. [Content Brief]

[15]. A Rodríguez-Hernández, et al. Nuclear caspase-3 and caspase-7 activation, and poly(ADP-ribose) polymerase cleavage are early events in camptothecin-induced apoptosis. Apoptosis. 2006 Jan;11(1):131-9. [Content Brief]

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