14-3-3 sigma
The gene called 14-3-3 sigma was found through quantitative analysis of expression patterns in colorectal cancer cell lines. 14-3-3 sigma is strongly induced by gamma irradiation and other DNA damaging agents. Induction of 14-3-3 sigma is mediated by a p53-responsive enhancer element. Like its fission-yeast homologues, rad24 and rad25, 14-3-3 sigma is involved in G2/M checkpoint control (Hermeking et al., 1997, Mol. Cell, 1(1):3-11).

Serial Analysis of Gene Expression (SAGE)allows the quantitative and simultaneous analysis of all the transcripts within the so-called transcriptome of a cell . A cDNA library is prepared from tissue or a cell line - short diagnostic sequence tags (about 10 bp long) are isolated from each of the cDNAs within this cDNA library by a sophisticated genetic manipulation - the sequence tags are concatenated by ligation - the concatamers are cloned into a plasmid vector - sequencing of the concatamers reveals the sequence of the tags - the 10 bp tag sequence is usually sufficient to identify the corresponding cDNA from which the tag originated - sequencing of 50,000 to 100,000 of those tags reveales a gene expression pattern characteristic of the cell sample examined (Valculescu et al., 1995, Science, 270(5235): 484) .

SAM domain
The Sterile Alpha Motif (SAM) domain is a protein interaction module that is present in diverse signal-transducing proteins such as the Eph family of receptor tyrosine kinases, diacylglycerol kinases, serine-threonine kinases, Src homology 2 (SH2) domain-containing adapter proteins, and others. Also the apoptosis regulator protein BAR contains a SAM domain (Thanos et al., 1999, Science, 283: 833-836).

Smad Anchor for Receptor Activation (SARA), an anchor protein that recruits Smad2 and Smad3 to the TGF-beta receptor.

Malignant tumors that arise from connective tissues or muscle cells are termed sarcomas.

Scythe has been isolated in a GST pulldown experiment using Drosophila Reaper protein as a bait in a Xenopus laevis extract system. The interaction between Reaper and Scythe induces cytochrome c release from mitochondira and induction of nuclear apoptotic events. A deletion mutant of Scythe itself possesses dominant apoptosis inducing activity (in the absence of Reaper), and it had been proposed that the pro-apoptotic activity of wildtype Scythe might be triggered by the interaction with a Reaper(-like) protein, causing Scythe to adopt a certain conformation which corresponds to that of the Scythe deletion mutant. The pro-apoptotic activity of Scythe depends on the presence of additional cytosolic accessory factors which supposedly are released from Scythe upon its interaction with Reaper(-like) protein. Scythe has also been reported to bind to two other Drosophila apoptotic regulators, Grim and Hid.. Up to now, no Scythe orthologs have been identified in vertebrate cells (Thress et al., 1998, EMBO, .17(.21):6135-6143; Thress et al., 1999, EMBO, 18(20): 5486-5493).

Selective estrogen receptor modulators (SERMs) are agents that function as estrogen agonists in the tissues in which estrogen is beneficial (such as bone, brain, cardiovascular system) but that will function as estrogen antagonists in sites where estrogen may promote carcinogenesis, such as breast, uterus, or ovary. Tamoxifen and Raloxifene are examples for SERMs.

A family of serine protease inhibitors.

Systemic Lupus Erythematosus; autoimmune disease, antinuclear antibodies against blood cells and other tissues lead to the formation of soluble immune complexes which cause vascular inflammations.

Second Mitochondria-derived Activator of Caspases (Smac) was identified in biochemical experiments as a protein factor that promotes the activation aof caspase-3 by the apoptosome. It was demonstrated that Smac obviously removes inhibitor of apoptosis proteins, IAPs, from the caspase-3 activating machinery in cell extracts. Smac is a mitochondrial protein which is released into the cytosol upon apoptosis induction: the released form of Smac must be devoid of its N-terminal mitochondrial signaling sequence in order to be active in its pro-apoptotic function (Du et al., 2000, Cell, 102: 33-42, Verhagen et al., 2000, Cell, 102: 43-53), and the interaction between Smac and e.g. the XIAP BIR domain is dependent on the first four N-terminal amino acids behind the mitochondrial targeting sequence of Smac: AIVP.

Smads are pivotal to intracellular signalling by members of the TGF-beta family. Smad2 and Smad3 are receptor-regulated Smads that interact with, and become phosphorylated by, activated type-I receptor kinases. The phosphorylated Smad then binds Smad4, and this heteromeric complex is translocated to the nucleus where it controls the transcription of target genes which are leading to inhibition of proliferation in most normal cells. Smad was reported to induce p21waf1 expression. Smad/DPC4 is a tumor suppressor gene which is deleted or mutated in about 50% of pancreatic adenocarcinomas.

The Silencer of Death Domains (SODD) was isolated as a protein that prevents constitutive activation of TNF-R1. It interacts with the Death Domains of TNF-R1 and DR3 but not with those of Death Domain Receptors (DDRs) such as TNF-R2, Fas, DR4, or DR5. It was demonstrated that SODD interacts with a region of TNF-R1 that also interacts with TRADD. SODD and TNF-R1 are pre-associated in non-stimulated cells, and upon TNF treatment this SODD-TNF-R1 complex is rapidly disrupted. Overexpresion of SODD prevents TNF-induced cell death and activation of NF-kB Jiang et al, 1999, Science, 283: 543-46).

Guanine Nucleotide Exchange Factor which binds to Grb2 and then activates Ras by facilitating GDP/GTP exchange.

Signal Transducer and Activator of Transcription (STAT) are important in cytokine signaling, activated by Tyr phosphorylation by JAKs following to binding of cytokine to its receptor (e.g. EGF, PDGF, insulin). Phosphorylated STATs form homo- or heterodimers through SH2 domains and translocate into the nucleus and induce gene expression.

Sulindac is a nonselective COX inhibitor, reported to suppress colon adenoma formation, presumably by inducing apoptosis in a BAX-dependent, p53-independent mode of action by downregulating Bcl-XL (Zhang et al., 2000, Science 290: 989).

Survivin is a member of the human IAPs. Elevated survivin expression was reported in most human tumors. In HeLa cells, survivin was found to be expressed in the G2/M phase of the cell cycle in a cycle regulated manner and to associate with the microtubuli of the mitotic spindle in a specific and saturable reaction. Disruption of survivin-microtubuli interactions resulted in loss of anti-apoptotic activity of survivin and increased caspase-3 activation. Survivin may be required to counteract a constitutive pathway that induces apoptosis during mitosis (Li et al., 1998, Nature, 396: 580-84). More...

Many enveloped viruses possess a fusion protein in their envelopes which confers the ability of the virion to fuse with the host cell membrane and thus allows entry of the infectious genomic material into the cell cytoplasm. During replication of the virus, expression of the fusion protein at the cell membrane can result in the fusion of neighbouring cells and the formation of multi-nucleate cells, also called syncytia. Syncytia plays a role in cell death induced by HIV.

SV40 T
The Simian virus large T antigen is a single dual purpose protein able to block both Rb and p53.

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