Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ZBP-89 induces apoptosis in human gastrointestinal cancer cells through a p53-independent mechanism. To understand the apoptotic pathway regulated by ZBP-89, we identified downstream signal transduction targets. Ectopic expression of ZBP-89 induced apoptosis through the mitochondrial pathway and was accompanied by activation of all three MAP kinase subfamilies: JNK1/2, ERK1/2 and p38 MAP kinase. ZBP-89-induced apoptosis was markedly enhanced by ERK inhibition with U0126. In contrast, inhibiting JNK with a JNK1-specific peptide inhibitor or dominant-negative JNK2 expression abrogated ZBP-89-mediated apoptosis. The p38 inhibitor SB202190 had no effect on ZBP-89-induced cell death. Protein dephosphorylation assays revealed that ZBP-89 activates JNK via repression of JNK dephosphorylation. Oligonucleotide microarray analyses revealed that ectopic expression of ZBP-89 downregulated expression of the dual-specificity phosphatase MKP6. Overexpression of MKP6 blocked ZBP-89-induced JNK phosphorylation and PARP cleavage. In addition, ectopic expression of ZBP-89 repressed Bcl-xL and Mcl-1 expression, but had no effect on Bcl-2. Silencing ZBP-89 with small interfering RNA enhanced both Bcl-xL and Mcl-1 expression. Taken together, ZBP-89-mediated apoptosis occurs via a p53-independent mechanism that requires JNK activation.
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PMID:ZBP-89-induced apoptosis is p53-independent and requires JNK. 1496 12

The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.
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PMID:The Helicobacter pylori virulence factor CagA promotes Erk1/2-mediated Bad phosphorylation in lymphocytes: a mechanism of CagA-inhibited lymphocyte apoptosis. 1714 Apr 4