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Pathway Description
D4-GDI Signaling Pathway
Bos taurus
Category:
Protein Pathway
Sub-Categories:
Apoptosis Signaling
Cytoskeletal Signaling
Cellular Response
Created: 2018-09-20
Last Updated: 2019-08-16
Perforin protein forms pores in the membrane to allow for granzyme B to enter the cell. Granzymes induce apoptosis by activating caspases. D4-GDP dissociation inhibitor (D4-GDI) is a negative regulator of ras-related Rho Family of GTPases. D4-GDI binds Rho GTPases to keep the Rho protein in a GDP-bound and inactivate state. Caspase 3 cleaves D4-GDI into two fragments of 5 kDa and 23 kDa size. The 23 kDa fragment translocates to the nucleus to activate Jun kinase, a regulator of apoptosis. Poly (ADP-ribose) polymerase-1 (PARP) is a substrate for caspase-3. Caspase-3 cleaves PARP into various fragments, this is a hallmark of apoptosis. PARP functions to detect and repair DNA damage. Cleavage of PARP by caspase prevents DNA repair, contributing to cell death. RHO GTPases become activated when released from D4-GDI upon cleavage by caspase-3. RHO GTPases mediate cytoskeleton changes leading to apoptosis and cell death. .
References
D4-GDI Signaling Pathway References
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Pubmed: 5933874
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Pubmed: 16866357
Yu H, Lee I, Salomon AR, Yu K, Huttemann M: Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):1066-71. doi: 10.1016/j.bbabio.2008.04.023. Epub 2008 Apr 22.
Pubmed: 18471988
Humke EW, Ni J, Dixit VM: ERICE, a novel FLICE-activatable caspase. J Biol Chem. 1998 Jun 19;273(25):15702-7. doi: 10.1074/jbc.273.25.15702.
Pubmed: 9624166
Koenig U, Eckhart L, Tschachler E: Evidence that caspase-13 is not a human but a bovine gene. Biochem Biophys Res Commun. 2001 Aug 3;285(5):1150-4. doi: 10.1006/bbrc.2001.5315.
Pubmed: 11478774
Davis AR, Clements MK, Bunger PL, Siemsen DW, Quinn MT: Cloning and characterization of bovine low molecular weight GTPases (Rac1 and Rac2) and rho GDP-dissociation inhibitor 2 (D4-GDI). Vet Immunol Immunopathol. 2000 May 23;74(3-4):285-301.
Pubmed: 10802295
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Pubmed: 19390049
Saito I, Hatakeyama K, Kido T, Ohkubo H, Nakanishi S, Ueda K: Cloning of a full-length cDNA encoding bovine thymus poly(ADP-ribose) synthetase: evolutionarily conserved segments and their potential functions. Gene. 1990 Jun 15;90(2):249-54. doi: 10.1016/0378-1119(90)90187-v.
Pubmed: 2119324
Taniguchi T, Yamauchi K, Yamamoto T, Toyoshima K, Harada N, Tanaka H, Takahashi S, Yamamoto H, Fujimoto S: Depression in gene expression for poly(ADP-ribose) synthetase during the interferon-gamma-induced activation process of murine macrophage tumor cells. Eur J Biochem. 1988 Feb 1;171(3):571-5. doi: 10.1111/j.1432-1033.1988.tb13826.x.
Pubmed: 2450019
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0066935
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