Among all species, caspase-2 (C2) is the most evolutionarily conserved caspase required for effective initiation of apoptosis following death stimuli. C2 is activated through dimerization and autoproteolytic cleavage and inhibited through phosphorylation at Ser139 and Ser164 , within the linker between the caspase recruitment and p19 domains of the zymogen, followed by association with the adaptor protein 14-3-3, which maintains C2 in its immature form procaspase (proC2). However, the mechanism of 14-3-3-dependent inhibition of C2 activation remains unclear. Here, we report the structural characterization of the complex between proC2 and 14-3-3 by hydrogen/deuterium mass spectrometry and protein crystallography to determine the molecular basis for 14-3-3-mediated inhibition of C2 activation. Our data reveal that the 14-3-3 dimer interacts with proC2 not only through ligand-binding grooves but also through other regions outside the central channel, thus explaining the isoform-dependent specificity of 14-3-3 protein binding to proC2 and the substantially higher binding affinity of 14-3-3 protein to proC2 than to the doubly phosphorylated peptide. The formation of the complex between 14-3-3 protein and proC2 does not induce any large conformational change in proC2. Furthermore, 14-3-3 protein interacts with and masks both the nuclear localization sequence and the C-terminal region of the p12 domain of proC2 through transient interactions in which both the p19 and p12 domains of proC2 are not firmly docked onto the surface of 14-3-3. This masked region of p12 domain is involved in C2 dimerization. Therefore, 14-3-3 protein likely inhibits proC2 activation by blocking its dimerization surface. DATABASES: Structural data are available in the Protein Data Bank under the accession numbers 6SAD and 6S9K.

• Klíčová slova
• 14-3-3 protein, H/D exchange, caspase-2, crystallography, protein-protein interaction,
• MeSH
• fosforylace MeSH
• kaspasa 2 chemie   genetika   metabolismus   MeSH
• konformace proteinů * MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární modely * MeSH
• multimerizace proteinu * MeSH
• mutace MeSH
• protein - isoformy genetika   metabolismus   MeSH
• proteinové prekurzory chemie   genetika   metabolismus   MeSH
• proteiny 14-3-3 chemie   genetika   metabolismus   MeSH
• rekombinantní proteiny chemie   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kaspasa 2 MeSH
• protein - isoformy MeSH
• proteinové prekurzory MeSH
• proteiny 14-3-3 MeSH
• rekombinantní proteiny MeSH

Caspase-2 is an apical protease responsible for the proteolysis of cellular substrates directly involved in mediating apoptotic signaling cascades. Caspase-2 activation is inhibited by phosphorylation followed by binding to the scaffolding protein 14-3-3, which recognizes two phosphoserines located in the linker between the caspase recruitment domain and the p19 domains of the caspase-2 zymogen. However, the structural details of this interaction and the exact role of 14-3-3 in the regulation of caspase-2 activation remain unclear. Moreover, the caspase-2 region with both 14-3-3-binding motifs also contains the nuclear localization sequence (NLS), thus suggesting that 14-3-3 binding may regulate the subcellular localization of caspase-2. Here, we report a structural analysis of the 14-3-3ζ:caspase-2 complex using a combined approach based on small angle X-ray scattering, NMR, chemical cross-linking, and fluorescence spectroscopy. The structural model proposed in this study suggests that phosphorylated caspase-2 and 14-3-3ζ form a compact and rigid complex in which the p19 and the p12 domains of caspase-2 are positioned within the central channel of the 14-3-3 dimer and stabilized through interactions with the C-terminal helices of both 14-3-3ζ protomers. In this conformation, the surface of the p12 domain, which is involved in caspase-2 activation by dimerization, is sterically occluded by the 14-3-3 dimer, thereby likely preventing caspase-2 activation. In addition, 14-3-3 protein binding to caspase-2 masks its NLS. Therefore, our results suggest that 14-3-3 protein binding to caspase-2 may play a key role in regulating caspase-2 activation. DATABASE: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.ww pdb.org (PDB ID codes 6GKF and 6GKG).

• Klíčová slova
• 14-3-3 protein, caspase-2, fluorescence, nuclear localization sequence, protein-protein interactions, small angle X-ray scattering,
• MeSH
• cysteinové endopeptidasy chemie   metabolismus   MeSH
• fosforylace MeSH
• jaderné lokalizační signály * MeSH
• kaspasa 2 chemie   metabolismus   MeSH
• konformace proteinů MeSH
• lidé MeSH
• maloúhlový rozptyl MeSH
• molekulární modely MeSH
• proteiny 14-3-3 chemie   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CASP2 protein, human MeSH Prohlížeč
• cysteinové endopeptidasy MeSH
• jaderné lokalizační signály * MeSH
• kaspasa 2 MeSH
• proteiny 14-3-3 MeSH

Procaspase-2 phosphorylation at several residues prevents its activation and blocks apoptosis. This process involves procaspase-2 phosphorylation at S164 and its binding to the scaffolding protein 14-3-3. However, bioinformatics analysis has suggested that a second phosphoserine-containing motif may also be required for 14-3-3 binding. In this study, we show that human procaspase-2 interaction with 14-3-3 is governed by phosphorylation at both S139 and S164. Using biochemical and biophysical approaches, we show that doubly phosphorylated procaspase-2 and 14-3-3 form an equimolar complex with a dissociation constant in the nanomolar range. Furthermore, our data indicate that other regions of procaspase-2, in addition to phosphorylation motifs, may be involved in the interaction with 14-3-3.

• Klíčová slova
• 14-3-3, Caspase-2, Phosphorylation, Procaspase-2, Protein-protein interaction,
• MeSH
• fosforylace MeSH
• kaspasa 2 chemie   metabolismus   MeSH
• lidé MeSH
• proteinové domény MeSH
• proteiny 14-3-3 metabolismus   MeSH
• rekombinantní proteiny chemie   metabolismus   MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kaspasa 2 MeSH
• proteiny 14-3-3 MeSH
• rekombinantní proteiny MeSH

AIM: A role of caspase-2 in chemotherapy-induced apoptosis has been suggested. Our study aimed to evaluate the prognostic and predictive importance of caspase-2 isoforms in breast cancer patients. MATERIALS & METHODS: Caspase-2L and -2S transcript levels were determined in paired tumor and non-malignant control tissues from 64 patients after neoadjuvant chemotherapy and 100 pretreatment patients (general set) by real-time PCR with absolute quantification. RESULTS: Low but statistically significant upregulation of caspase-2L in tumor versus control tissues was observed in both sets. Significant associations of the levels of caspase-2L, -2S or S/L ratio with clinical prognostic factors were observed. However, none of these associations were confirmed in both sets. Levels of caspase-2 isoforms or the S/L ratio did not significantly associate with progression-free survival in the general set or with chemotherapy response in the neoadjuvant set. CONCLUSION: Our results suggest that the role of caspase-2 isoforms in the progression of breast cancer may considerably differ between pre- and post-chemotherapy patients.

• MeSH
• adjuvantní chemoterapie MeSH
• cysteinové endopeptidasy genetika   metabolismus   MeSH
• dospělí MeSH
• duktální karcinom prsu enzymologie   mortalita   MeSH
• frekvence genu MeSH
• izoenzymy genetika   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• kaspasa 2 genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádory prsu enzymologie   mortalita   MeSH
• neoadjuvantní terapie MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CASP2 protein, human MeSH Prohlížeč
• cysteinové endopeptidasy MeSH
• izoenzymy MeSH
• kaspasa 2 MeSH
• messenger RNA MeSH

BACKGROUND: Fatty acid-induced apoptosis and ER stress of pancreatic β-cells contribute to the development of type 2 diabetes, however, the molecular mechanisms involved are unclear. AIMS: In this study we have tested the role of caspase-2 and suggested ER stress mediator JNK in saturated fatty acid-induced apoptosis of the human pancreatic β-cells NES2Y. RESULTS: We found that stearic acid at apoptosis-inducing concentration activated ER stress signaling pathways, i.e. IRE1α, PERK and ATF6 pathways, in NES2Y cells. During stearic acid-induced apoptosis, JNK inhibition did not decrease the rate of apoptosis nor the activation of caspase-8, -9, -7 and -2 and PARP cleavage. In addition, inhibition of JNK activity did not affect CHOP expression although it did decrease the induction of BiP expression after stearic acid treatment. Caspase-2 silencing had no effect on PARP as well as caspase-8, -9 and -7 cleavage and the induction of CHOP expression, however, it also decreased the induction of BiP expression. Surprisingly, caspase-2 silencing was accompanied by increased phosphorylation of c-Jun. CONCLUSIONS: We have demonstrated that caspase-2 as well as JNK are not key players in apoptosis induction by saturated fatty acids in human pancreatic β-cells NES2Y. However, they appear to be involved in the modulation of saturated fatty acid-induced ER stress signaling, probably by a mechanism independent of c-Jun phosphorylation.

• MeSH
• apoptóza účinky léků   MeSH
• beta-buňky cytologie   metabolismus   MeSH
• chaperon endoplazmatického retikula BiP MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fosforylace MeSH
• JNK mitogenem aktivované proteinkinasy antagonisté a inhibitory   metabolismus   MeSH
• kaspasa 2 chemie   genetika   metabolismus   MeSH
• kaspasa 7 metabolismus   MeSH
• kaspasa 8 metabolismus   MeSH
• kaspasa 9 metabolismus   MeSH
• kyseliny stearové farmakologie   MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• poly(ADP-ribosa)-polymerasy metabolismus   MeSH
• proteiny tepelného šoku metabolismus   MeSH
• RNA interference MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• transkripční faktor ATF6 metabolismus   MeSH
• transkripční faktor CHOP metabolismus   MeSH
• transkripční faktory RFX MeSH
• transkripční faktory genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ATF6 protein, human MeSH Prohlížeč
• chaperon endoplazmatického retikula BiP MeSH
• DDIT3 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• JNK mitogenem aktivované proteinkinasy MeSH
• kaspasa 2 MeSH
• kaspasa 7 MeSH
• kaspasa 8 MeSH
• kaspasa 9 MeSH
• kyseliny stearové MeSH
• malá interferující RNA MeSH
• poly(ADP-ribosa)-polymerasy MeSH
• proteiny tepelného šoku MeSH
• stearic acid MeSH Prohlížeč
• transkripční faktor ATF6 MeSH
• transkripční faktor CHOP MeSH
• transkripční faktory RFX MeSH
• transkripční faktory MeSH

We have analyzed the molecular mechanisms of photoinduced cell death using porphyrins with similar structure differing only in the position of the ethylene glycol (EG) chain on the phenyl ring. Meta- and para-positioned EG chains targeted porphyrins to different subcellular compartments. After photoactivation, both types of derivatives induced death of tumor cells via reactive oxygen species (ROS). Para derivatives pTPP(EG)4 and pTPPF(EG)4 primarily accumulated in lysosomes activated the p38 MAP kinase cascade, which in turn induced the mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG)4 localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca(2+) homeostasis manifested by Ca(2+) rise in the cytoplasm, activation of calpains and stress caspase-12 or caspase-4. ER stress developed into unfolded protein response. Immediately after irradiation the PERK pathway was activated through phosphorylation of PERK, eIF2α and induction of transcription factors ATF4 and CHOP, which regulate stress response genes. PERK knockdown and PERK deficiency protected cells against mTPP(EG)4-mediated apoptosis, confirming the causative role of the PERK pathway.

• MeSH
• apoptóza účinky léků   účinky záření   MeSH
• ethylenglykol chemie   MeSH
• fotochemoterapie * MeSH
• genový knockdown MeSH
• homeostáza účinky léků   účinky záření   MeSH
• iniciační kaspasy metabolismus   MeSH
• kaspasa 2 metabolismus   MeSH
• kinasa eIF-2 nedostatek   genetika   metabolismus   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• nádorové buněčné linie MeSH
• porfyriny chemie   farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce účinky léků   účinky záření   MeSH
• stres endoplazmatického retikula účinky léků   účinky záření   MeSH
• subcelulární frakce účinky léků   metabolismus   účinky záření   MeSH
• vápník metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CASP4 protein, human MeSH Prohlížeč
• ethylenglykol MeSH
• iniciační kaspasy MeSH
• kaspasa 2 MeSH
• kinasa eIF-2 MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• PERK kinase MeSH Prohlížeč
• porfyriny MeSH
• reaktivní formy kyslíku MeSH
• vápník MeSH

Various DNA-targeting agents may initiate p53-dependent as well as p53-independent response and subsequent apoptosis via alternative cellular systems which include for instance p73, caspase-2 or Bcl-2 family proteins. The scope of involvement of individual molecules in this process and the mechanisms governing their potential interplay are still not entirely understood, in particular in highly aggressive cancers such as in malignant melanoma. In this work we investigated the role and involvement of both p53-dependent and -independent mechanisms in selected melanoma cell lines with differing status of p53 using a model DNA topoisomerase I inhibitor camptothecin (CPT). Here we report that CPT induced in Bowes melanoma cells apoptosis which is essentially p53 and mitochondria-dependent but with some involvement of caspase-2 and p73. Conversely, in mutant p53 melanoma cells overall levels of CPT-induced apoptosis are significantly lower, with p73 and caspase-2 signaling playing important roles. In addition, in these cells the expression of micro RNAs family 34 (miR-34) were low compared to wild-type p53 cells. The ectopic expression of wild type p53 than restored apoptotic response of cells to CPT despite the fact that the expression of miR-34 and miR-155 were not influenced. These results suggest that CPT induces multivariate cellular stress responses including activation of DNA-damage response-p53 pathway as well as p53-independent signaling and their mutual crosstalk play the decisive role in the efficient triggering of apoptosis in melanoma cells.

• MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   MeSH
• cysteinové endopeptidasy genetika   metabolismus   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• inhibitory topoisomerasy I farmakologie   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• kamptothecin farmakologie   MeSH
• kaspasa 2 genetika   metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• melanom genetika   metabolismus   patologie   MeSH
• mikro RNA genetika   metabolismus   MeSH
• mitochondrie účinky léků   genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• poškození DNA účinky léků   MeSH
• protein p73 MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• CASP2 protein, human MeSH Prohlížeč
• cysteinové endopeptidasy MeSH
• DNA vazebné proteiny MeSH
• inhibitory topoisomerasy I MeSH
• jaderné proteiny MeSH
• kamptothecin MeSH
• kaspasa 2 MeSH
• mikro RNA MeSH
• nádorové supresorové proteiny MeSH
• nádorový supresorový protein p53 MeSH
• protein p73 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• TP73 protein, human MeSH Prohlížeč

Despite the reported cytotoxicity and apoptosis-inducing properties of sulforaphane (SF) in colon cancer cells, the details concerning individual mechanisms and signaling cascades underlying SF-mediated apoptosis remain unclear. To understand different aspects of SF-induced proapoptic signaling in advanced colon carcinoma, we investigated its mechanisms in metastatic SW620 cell line. Our results indicate that in SW620 cells SF acts to induce multivariate cascades including DNA-damage response pathway whose proapoptotic signaling is nevertheless reduced owing to the mutant status of p53 and caspase-2-JNK pathway which seems to complement and enhance p53-dependent signaling, however only in wild-type p53. Furthermore, both pathways require the active role of mitochondria and do not depend on generation of ROS, making SF an attractive chemopreventive agent whose antitumor properties should be further investigated in colon cancer.

• MeSH
• antikarcinogenní látky farmakologie   MeSH
• apoptóza účinky léků   MeSH
• cytochromy c metabolismus   MeSH
• isothiokyanatany MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• kaspasa 2 metabolismus   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory tračníku farmakoterapie   metabolismus   patologie   MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA MeSH
• sulfoxidy MeSH
• thiokyanatany farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikarcinogenní látky MeSH
• cytochromy c MeSH
• isothiokyanatany MeSH
• JNK mitogenem aktivované proteinkinasy MeSH
• kaspasa 2 MeSH
• nádorový supresorový protein p53 MeSH
• sulforaphane MeSH Prohlížeč
• sulfoxidy MeSH
• thiokyanatany MeSH

BACKGROUND: In this study, the effect of novel taxane SB-T-1216 and paclitaxel on sensitive MDA-MB-435 and resistant NCI/ADR-RES human breast cancer cells was compared. MATERIALS AND METHODS: Cell growth and survival were evaluated after 96-hour incubation with tested concentrations of taxanes. The effect on the formation of microtubule bundles was assessed employing fluorescence microscopy and on the cell cycle employing flow cytometric analysis. The activity of caspases was assessed employing commercial colorimetric kits. RESULTS: The IC(50) (concentration resulting in 50% of living cells in comparison with the control) of SB-T-1216 in sensitive cells was 0.6 nM versus 1 nM for paclitaxel. However, the IC(50) of SB-T-1216 in resistant cells was 1.8 nM versus 300 nM for paclitaxel. Both SB-T-1216 and paclitaxel at death-inducing concentrations induced the formation of microtubule bundles in sensitive as well as resistant cells. Cell death induced in sensitive and resistant cells by paclitaxel was associated with the accumulation of cells in the G(2)/M phase. On the contrary, cell death induced by SB-T-1216 took place without the accumulation of cells in the G(2)/M phase but with a decreased number of G(1) cells and the accumulation of hypodiploid cells. Both SB-T-1216 and paclitaxel activated caspase-3, caspase-9, caspase-2 and caspase-8 in sensitive as well as resistant cells. CONCLUSION: Cell death induced by both paclitaxel and novel taxane SB-T-1216 in breast cancer cells is associated with caspase activation and with the formation of interphase microtubule bundles. Novel taxane SB-T-1216, but not paclitaxel, seems to be capable of inducing cell death without the accumulation of cells in the G(2)/M phase.

• MeSH
• antibiotika antitumorózní farmakologie   MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buněčné dělení účinky léků   MeSH
• chemorezistence MeSH
• doxorubicin farmakologie   MeSH
• fluorescenční mikroskopie MeSH
• G1 fáze účinky léků   MeSH
• G2 fáze účinky léků   MeSH
• kaspasa 2 metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 8 metabolismus   MeSH
• kaspasa 9 metabolismus   MeSH
• lidé MeSH
• mikrotubuly účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• paclitaxel farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• taxoidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• antitumorózní látky fytogenní MeSH
• doxorubicin MeSH
• kaspasa 2 MeSH
• kaspasa 3 MeSH
• kaspasa 8 MeSH
• kaspasa 9 MeSH
• paclitaxel MeSH
• taxoidy MeSH

Cytotoxicity and apoptosis induced by etoposide were studied during 72 hr in human melanoma cells. Etoposide initiated DNA-damage signaling via ATM kinase and activated p53 pathway and caspase-2. In response to treatment with etoposide, mitochondria of melanoma cells first increased their abundance and activity, and at later treatment intervals their dynamic behavior and functions became suppressed. Observed mitochondrial perturbation was not preceded by membrane potential loss but cytochrome c release was observed together with a rise in caspase-9 and caspase-3 activities. The pharmacological inhibition of relevant induced targets proved the importance of ATM and caspase-2 in etoposide-mediated cytotoxicity and apoptosis.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   MeSH
• ATM protein MeSH
• benzothiazoly farmakologie   MeSH
• cyklosporin farmakologie   MeSH
• cysteinové endopeptidasy metabolismus   MeSH
• DNA vazebné proteiny antagonisté a inhibitory   metabolismus   MeSH
• etoposid farmakologie   MeSH
• inhibitory cysteinových proteinas farmakologie   MeSH
• inhibitory kaspas MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kaspasa 2 metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 9 metabolismus   MeSH
• lidé MeSH
• melanom patologie   MeSH
• mitochondrie účinky léků   MeSH
• nádorové buňky kultivované účinky léků   MeSH
• nádorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• nádorové supresorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• poškození DNA MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   metabolismus   MeSH
• proteiny buněčného cyklu antagonisté a inhibitory   metabolismus   MeSH
• superoxidy metabolismus   MeSH
• toluen analogy a deriváty   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• antitumorózní látky fytogenní MeSH
• ATM protein, human MeSH Prohlížeč
• ATM protein MeSH
• BAX protein, human MeSH Prohlížeč
• benzothiazoly MeSH
• CASP2 protein, human MeSH Prohlížeč
• cyklosporin MeSH
• cysteinové endopeptidasy MeSH
• DNA vazebné proteiny MeSH
• etoposid MeSH
• inhibitory cysteinových proteinas MeSH
• inhibitory kaspas MeSH
• inhibitory proteinkinas MeSH
• kaspasa 2 MeSH
• kaspasa 3 MeSH
• kaspasa 9 MeSH
• nádorové proteiny MeSH
• nádorové supresorové proteiny MeSH
• nádorový supresorový protein p53 MeSH
• pifithrin MeSH Prohlížeč
• protein X asociovaný s bcl-2 MeSH
• protein-serin-threoninkinasy MeSH
• proteiny buněčného cyklu MeSH
• superoxidy MeSH
• toluen MeSH