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Apoptosis

程序化细胞死亡或细胞凋亡是多细胞生物体的重要生理过程。细胞生长分裂和细胞死亡速度之间的均衡能够根据内部或外部参数动态调整细胞数量。例如,在脊椎动物的神经系统发育过程中,大约有一半的细胞在形成后不久就凋亡。在成年生物体中,这种平衡对于保持器官和组织的大小和功能等非常重要。此类平衡调节异常时常会导致癌症。细胞凋亡与细胞坏死不同。细胞坏死是指受影响的细胞破裂后,导致可能的损害性炎症反应,而细胞凋亡呈现为非常有组织的方式:细胞收缩凝集,内部结构分解,DNA 断裂为碎片。然后,周围的细胞或巨噬细胞迅速吞噬死亡细胞。

凋亡过程的核心是 caspase,一种半胱氨酸蛋白酶家族。它们生成为酶前体,由其他 caspase 转化为活性后裂解。当起始酶前体(例如酶前体 8、9、10)在接头蛋白的帮助下聚合时,触发此 caspase 级联反应,从而促进相互激活,减少低蛋白酶活性或酶前体构象变化的影响。已激活的 caspase 之后自由激活效应 caspase(例如 caspase 3、6 和 7),促进细胞凋亡。它们的效果进一步受 Bcl-2 家族蛋白质(例如 Bcl-2、Bcl-xL)和 IAP(细胞凋亡抑制剂,例如 BIRC1、XIAP)控制。

细胞凋亡过程遵循若干途径。外源性死亡受体途径通过配体诱导,这些配体结合到含有胞质死亡域的死亡受体蛋白家族(例如 FAS 和 TRAIL 受体)。内源性途径则是响应 DNA 损坏或线粒体应力,与癌症特别相关。除了这些标准细胞凋亡途径外,还有 caspase 非依赖性途径,由粒酶 B 和粒酶 A 等触发。这些 caspase 非依赖性途径已针对抑制 caspase 的病毒产生进化。

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Caspases

Mitochondrial

BCL2 (B-Cell CLL/lymphoma 2):

This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends. [provided by...   更多...

BCL2L1 (BCL2-Like 1):

The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC...   更多...

Inhibitor of Apoptosis

BIRC2 (Baculoviral IAP Repeat Containing 2):

The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants...   更多...

EPR1 (Early-Phytochrome-Responsive1):

Receptor

CRADD (CASP2 and RIPK1 Domain Containing Adaptor with Death Domain):

DR4 (Drought-Repressed 4 Protein):

RIPK1 (Receptor (TNFRSF)-Interacting serine-threonine Kinase 1):

TRAF1 (TNF Receptor-Associated Factor 1):

TRAF2 (TNF Receptor-Associated Factor 2):

TNFRSF10C (Tumor Necrosis Factor Receptor Superfamily, Member 10c, Decoy Without An Intracellular Domain):

TNFRSF10D (Tumor Necrosis Factor Receptor Superfamily, Member 10d, Decoy with Truncated Death Domain):

Cytoplasmatic

YWHAQ (Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein, theta Polypeptide):

YWHAZ (Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein, zeta Polypeptide):

Endoplasmatic Reticulum

CAPNL1 (Calpain 1, Large Subunit):

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme,...   更多...

TREX1 (three Prime Repair Exonuclease 1):

This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep...   更多...

SET (SET Nuclear Oncogene):

Granzyme

Gzmb - GZMB

Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein encoded by this gene is crucial for the rapid induction of...

GZMA (Granzyme A (Granzyme 1, Cytotoxic T-Lymphocyte-Associated serine Esterase 3)):

Nuclear

PARP1 (Poly (ADP-Ribose) Polymerase 1):

This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery...   更多...

AIFM1 (Apoptosis-Inducing Factor, Mitochondrion-Associated, 1):

DFFB (DNA Fragmentation Factor, 40kDa, beta Polypeptide (Caspase-Activated DNase)):

DNA damage

ABL1 (C-Abl Oncogene 1, Non-Receptor tyrosine Kinase):

The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9\;22) translocation results in the head-to-tail fusion of the...   更多...

ATR (Ataxia Telangiectasia and Rad3 Related):

TRIM29 (Tripartite Motif Containing 29):

Apoptosis Markers

ANXA5 - Annexin V

The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth...   更多...

AIFM1 (Apoptosis-Inducing Factor, Mitochondrion-Associated, 1):

EPR1 (Early-Phytochrome-Responsive1):

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