Xiaodong Wang's research while affiliated with University of Texas Southwestern Medical Center and other places

Publications (10)

Article
Full-text available
Following cleavage by caspase 8, the C-terminus of Bid translocates from the cytosol to the mitochondria that is dependent upon structures formed by the mitochondrial-specific lipid cardiolipin. Once associated with mitochondria, truncated Bid (tBid) causes the potent release of cytochrome c, endonuclease G, and smac. We investigated whether tBid l...
Article
Apoptosis is an essential process in the development and homeostasis of all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell death by inhibiting the activity of caspases; this inhibition is performed by the zinc-binding BIR domains of the IAP proteins. The mitochondrial protein Smac/DIABLO promotes apoptosis by eliminating the inh...
Article
Granzyme B (GzmB) is a component of cytotoxic lymphocyte granules that can rapidly initiate apoptosis in target cells. While several procaspases are cleaved and activated by GzmB, the absolute requirement of caspase activation for GzmB-induced apoptosis is controversial. In this report, we demonstrate that GzmB can initiate apoptosis in the absence...
Article
Cytochrome c released from mitochondria has been proposed to be an essential component of an apoptotic pathway responsive to DNA damage and other forms of cell stress. Murine embryos devoid of cytochrome c die in utero by midgestation, but cell lines established from early cytochrome c null embryos are viable under conditions that compensate for de...
Article
Cell death via apoptosis is a prominent feature in mammalian neural development. Recent studies into the basic mechanism of apoptosis have revealed biochemical pathways that control and execute apoptosis in mammalian cells. Protein factors in these pathways play important roles during development in regulating the balance between neuronal life and...
Article
Full-text available
The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease complex critical for the induction of DNA fragmentation in vitro. To understand the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant mice. DNA fragmentation activity is completely abolished in cell extracts from DFF45 mutant tissues. In respons...
Article
We report here the purification of a cytosolic protein that induces cytochrome c release from mitochondria in response to caspase-8, the apical caspase activated by cell surface death receptors such as Fas and TNF. Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax. C...
Article
We report here the purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3. The NH2-terminal 85 amino acids of Apaf-1 show 21% identity and 53% similarity to the NH2-terminal prodomain of the Caenorhabditis elegans caspase, CED-3. This is followed...

Citations

... Another indirect source of evidence comes from the presence of synaptic material within microglial lysosomes observed via confocal, electron and super-resolution microscopy (Stevens et al., 2007;Paolicelli et al., 2011;Schafer et al., 2012Schafer et al., , 2014Weinhard et al., 2018). A caveat of these data is that it is possible that synaptic material found within microglia is a consequence of microglial uptake and clearance of debris from apoptotic neurons, which are commonplace during development (Nijhawan et al., 2000). Therefore, whether microglia actively prune synapses or merely 'clean up' is uncertain. ...
... Indeed, microinjection of Cyt c mutants further supports our conclusion that individual lysine residues play an important role in apoptogenic activity of Cyt c. The binding constant or binding of Cyt c with Apaf-1 characterizing WT Cyt c and Apaf-1 interaction has been previously reported using fluorescence polarization or gel filtration analyses [9,46]. The binding affinity for the WT Cyt c-Apaf-1 interaction is one order stronger than that observed in this study using ITC measurements. ...
... Inflammasomes can act as integral components of PANoptosomes, and ASC has been identified as a shared molecular feature [6,12,11,14]. Alternatively, apoptosis causes morphological membrane blebbing and cell shrinkage [20] and is molecularly controlled by either the formation of an apoptosome containing an adaptor APAF-1 and CASP9 or by the formation of a death-inducing signaling complex (DISC) containing a death receptor and CASP8; both activate the executioner caspases, CASP3 and CASP7 [21][22][23][24][25][26][27][28]. Necroptosis is another lytic innate immune cell death pathway initiated by the formation of a necrosome which contains RIPK1 and RIPK3. ...
... Inflammasomes can act as integral components of PANoptosomes, and ASC has been identified as a shared molecular feature [6,12,11,14]. Alternatively, apoptosis causes morphological membrane blebbing and cell shrinkage [20] and is molecularly controlled by either the formation of an apoptosome containing an adaptor APAF-1 and CASP9 or by the formation of a death-inducing signaling complex (DISC) containing a death receptor and CASP8; both activate the executioner caspases, CASP3 and CASP7 [21][22][23][24][25][26][27][28]. Necroptosis is another lytic innate immune cell death pathway initiated by the formation of a necrosome which contains RIPK1 and RIPK3. ...
... EndoGI; Zn 2+ (Counis and Torriglia, 2006;Li et al., 2001;Ruiz-Carrillo and Renaud, 1987;Widlak et al., 2001;Loll et al., 2009) a SerpinB1/MNEI/LEI is proteolytically processed to generate L-DnaseII. (Shiokawa and Tanuma, 2001;Napirei et al., 2000Napirei et al., , 2004Yasutomo et al., 2001;Lacks, 1981) Dnase1L1 (Pompe disease) b muscle weakness skeletal and cardiac muscle myocytes surface, lysosomes (Malferrari et al., 1999;Shiokawa et al., 2005Shiokawa et al., , 2007Los et al., 2000;Lichtenbelt et al., 2006) Dnase1L2 Parakeratosis; Psioriasis epidermis keratinocytes ER (Fischer et al., 2011(Fischer et al., , 2007 Dnase1L3 Pediatric-onset SLE spleen, liver macrophages, dendritic cells secreted, nucleus (Sisirak et al., 2016;Wilber et al., 2002;Napirei et al., 2005;Al-Mayouf et al., 2011;Errami et al., 2013) Dnase2a Embryonic lethal; Rheumatoid Arthritis; Lupus Nephritis most tissue, bone marrow macrophages lysosome (Kawane et al., 2001(Kawane et al., , 2006Shin et al., 2005;Rossol et al., 2009;Krieser et al., 2002) Dnase2b Cataracts lens, salivary gland, lungs fibre cells lysosome (Nishimoto et al., 2003) L-DnaseII Pseudomonas sensitivity bone marrow neutrophils nucleus (Benarafa et al., 2007;Torriglia et al., 2008) CAD Cancer ubiquitous ubiquitous nucleus (Enari et al., 1998;Liu et al., 1997;Zhang et al., 1998;Widlak and Garrard, 2005;Zhang et al., 1998;Yan et al., 2006) EndoG Cardiac Hypertrophy ubiquitous ubiquitous mitochondria/nucleus Widlak and Garrard, 2005;McDermott-Roe et al., 2011;Irvine et al., 2005) a Other tissues and cell types can also express these nucleases. b Controversial. ...
... The formation of QD clusters could sequester proteins, leading to a reduction in optimal protein levels for essential biological processes. Particularly, the deficiency of cytochrome c causes mitochondrial dysfunction, negatively impacts cellular metabolic pathways, and alters other essential biological processes [202][203][204][205][206]. Thus far, only a few types of plasma proteins have been tested. ...
... In a similar spirit, researchers found that releasing proapoptotic molecules from the mitochondria is necessary for granzyme B to activate caspase-3 [115]. DNA fragmentation can be induced by granzyme B, even in the absence of active caspases, by cleaving the nuclear caspase substrate inhibitor of caspase-activated DNase (ICAD), generating CAD and thereby bypassing the necessity for caspases [116][117][118][119]. Granzymes, a family of serine proteases, represents a key element of these cytotoxic granules. ...
... To assess overall (mitochondrial and extramitochondrial-dependent) PBMC apoptotic activation, caspase-3 activity was measured using the fluorimetric CaspACE Assay System (Promega, USA). This was based on the fluorimetric detection of amino-4-trifluoromethyl coumarin following proteolytic cleavage of the synthetic substrate DEVD-amino-4trifluoromethyl coumarin [16]. PBMC were homogeneized by 15 strokes of a 22G syringe in cell "lysis buffer" (25 mM Hepes, 5 mM MgCl2, 5mM EDTA, 5 mM DTT, 2mM PMSF, 10 μg/ml pepstatin A and 10 μg/ml leupeptin) followed by 3 cycles of freezing/thawing. ...
... 222,223 Because of their clinical significance, a lot of effort was devoted to the development of IAP antagonists, and the most promising small molecules targeting IAPs are mimetics of the N-terminal Ala-Val-Pro-Ile moiety of endogenous inhibitory IAP protein second mitochondria-derived activator of caspases (SMAC). 224,225 To get the best overview of the historical development of IAP antagonists, the authors suggest a review by Xing and Zhuang groups, 226 in which the four generations of SMACmimicking IAP antagonists were represented comprehensively and in a chronological manner. ...
... For mitochondrial fusion to take place, an ideal potential across the mitochondrial membrane is required. Mitochondrial fission factors are abnormally low in cancers [116]. When tumor tissue from lung cancer patients is compared to nearby healthy tissue, dynamin-related protein 1 (DRP1) levels increase and mitofusin 2 (MFN2) levels drop. ...