Apoptosis and Cancer signaling pathways Bcl-2 signaling in cellular apoptosis
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300_12_ED A&C Pathways Card:A4 18/05/2012 11:46 Page 1 Apoptosis and Cancer signaling pathways Bcl-2 signaling in cellular apoptosis p53 signaling in apoptosis and gene transcription Cellular stress, Death stimulus DNA damage Cellular stress p53 The bcl-2 family consist of pro- and anti-apoptotic proteins involved in intrinsic mitochondrial cell death. They regulate the release of apoptotic factors into the cytoplasm including cytochrome C and Apaf-1, by mediating outer membrane permeabilisation. This leads to activation of caspase-9 and the resulting caspase cascade. Bcl-2 inhibitors Caspase 3 Caspase 9 Gene G ene rregulation egulation eg n Bax Bcl-2 Mitochondria Apaf-1 Cyt-c Mitochondria Apoptosis Death receptor signaling in apoptosis and gene transcription Bcl-2 p53 is a critical tumour suppressive transcription factor which responds to cellular stress by triggering cell cycle arrest and apoptosis through transcriptional regulation. Cyt-c Apaf-1/Caspase 9 Cell cycle arrest, cell growth inhibition, metabolic stress inhibition Apoptosis Ap pop optos pto p pt to osis os Inhibitors of apoptosis signaling in cellular apoptosis TRAIL TNF• NF-κB Pathway Apoptosis Pathway DR4/5 TNFR1 receptors TNFR Caspase 8 ReIA Bid IIκB• Smac-mimetic (SH122) Death domain TRADD Mitochondria Smac IκB• FADD Death receptors (DRs) belong to the tumour necrosis factor (TNF) family of cytokines which induce apoptosis. These receptors can activate caspases within seconds causing apoptosis. Cyt-c Pro-caspase 8 BAX Caspase 3 Degradation Degr ad dation t TRAF-2 NF-κB BID Apoptosis IKK Transcription Inhibitors of apoptosis (IAPs) are a conserved group of proteins containing Baculovirus-IAP repeats involved in the regulation of apoptosis as well as a number of other cellular processes. XIAP cIAP-1 Cyt-c NF-κB Caspase 9 Caspase 3 PARP cleavage Apoptosis Discover more at abcam.com/biochemicals Copyright © 2012 Abcam, All Rights Reserved. 300_12_ED A&C Pathways Card:A4 18/05/2012 11:46 Page 2 Apoptosis and Cancer related products in the Abcam Biochemicals range: Product MAP kinases Anisomycin 2-Methoxyestradiol PD 98059 SB 202190 SB 203580 SB 203580 hydrochloride SL 327 SP600125 PD 0325901 PD 184352 U0126 CGP 57380 ZM 336372 Akt/PI3K SC-66 Luteolin LY 294002 Wortmannin Phorbol 12-myristate 13-acetate Ro 31-8220 mesylate Rottlerin Okadaic acid Biological description Protein synthesis inhibitor Potent anti-tumor and anti-angiogenic agent MEK1 inhibitor Highly selective, potent, cell permeable p38 MAP kinase inhibitor p38 MAP kinase inhibitor p38 MAP kinase inhibitor; water soluble MEK inhibitor JNK inhibitor Potent MEK 1 and 2 inhibitor Selective MEK inhibitor Selective MKK inhibitor MNK inhibitor Potent, selective c-Raf inhibitor Allosteric Akt inhibitor Antioxidant, anti-inflammatory, anti-cancer flavonoid PI3 kinase inhibitor PI3 kinase inhibitor PKC activator Protein kinase inhibitor Kinase inhibitor PP1 and PP2A inhibitor Purity Product code >98% >98% >99% >99% >99% >99% >99% >98% >99% >99% >98% >98% >98% ab120495 ab120653 ab120234 ab120638 ab120162 ab120235 ab120082 ab120065 ab120639 ab120641 ab120241 ab120365 ab120428 >99% >99% >99% >98% >99% >98% >95% >98% ab120802 ab120662 ab120243 ab120148 ab120297 ab120374 ab120377 ab120375 Product Biological description Purity Product code p53 Pifithrin-α-HBr p53 inhibitor >98% ab120478 Caspases Z-D(OMe)E(OMe)VD(OMe)-FMK Z-LE(OMe)VD(OMe)-FMK Z-VAD-FMK Cell permeable caspase-3 inhibitor Cell permeable derivative of caspase-4 inhibitor Z-LEVD-FMK Irreversible general caspase inhibitor >90% >90% >98% ab120488 ab120489 ab120382 Nitrogen oxide L-Arginine (S)-Nitrosoglutathione SNAP Spermidine hydrochloride 1400W Precursor to nitric oxide synthesis NO donor NO donor Endogenous polyamine. nNOS inhibitor. Selective iNOS inhibitor >99% >99% >99% ab120750 ab120285 ab120014 ab120057 ab120165 Calcium signaling K252a KN-62 Highly potent inhibitor of protein and CAM kinases CaM kinase II inhibitor. P2X7 antagonist. >99% >98% ab120419 ab120421 Cyclin-dependent kinase Purvalanol A Purvalanol B Potent CDK inhibitor CDK2 inhibitor >98% >98% ab120304 ab120305 GSK Phospho-Glycogen Synthase Peptide-2 SB 216763 GSK substrate Potent selective GSK-3 inhibitor >99% >98% ab120079 ab120202 Featured products Novel, selective, cell membrane permeable clathrin inhibitor. Competitively inhibits clathrin terminal domain to selectively inhibit clathrin mediated endocytosis (CME) (IC50 = 12 µM for inhibition of amphiphysin association of clathrin TD). Interferes with receptor mediated endocytosis (RME), entry of HIV and synaptic vesicle recycling. (ab120687) Structural domains of dynamin, their function and the target sites of action of the MiTMAB™, Dynole™ and Iminodyn™ chemical series collections Lipid Binding GTP Binding GTPase GTP Stalk PH AD PRD Domain Inhibitor Interaction GDP • Iminodyn-22™ • Dynole-34-2™ Ring Phos/Dephos Assembly Protein-Protein • MiTMAB™ • OcTMAB™ • RTIL-13™ World Exclusive! Dynamin inhibitors toolbox The Dynamin Inhibitors Toolbox (ab120468) is a unique collection of small molecule, potent and cell permeable dynamin inhibitors, enabling characterization of dynamin and endocytosis. The inhibitors have different mechanisms of action, target different domains of dynamin, and are based on differing chemical scaffolds. Negative controls for each chemical series are included. Discover more at abcam.com/biochemicals *Sold under exclusive licence from Children’s Medical Research Institute and Newcastle Innovation Ltd. Dynole-34-2™, Dynole-31-2™, MiTMAB™, OcTMAB™, Iminodyn-22™ and Iminodyn-17™ are trademarks of Children’s Medical Research Institute and Newcastle Innovation Ltd.” 300_12_ED World Exclusive! Pitstop 2™ Clathrin inhibitor
