Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The imbalance of cell pro-death and pro-survival signaling pathways determines the neuronal fate during cerebral ischemia/reperfusion (I/R) injury. However, the biological mechanisms regulating the balance between activation of the pro-death or the pro-survival signaling pathways remain unclear. In this study, a rat model of I/R injury was established using four-vessel occlusion followed by different times of reperfusion. I/R injury did not affect the level of FK506 binding protein 51 (FKBP51), PH domain and leucine rich repeat protein phosphatases (PHLPP)-2, and AKT, but induced assembly of the FKBP51-PHLPP2-AKT signaling complex, as indicated by the enhancement of interactions among these compounds following reperfusion. Using an antisense oligonucleotide, PHLPP2 expression was effectively inhibited. Critically, the inhibition of PHLPP2 prohibited the interactions of FKBP51, PHLPP2 and AKT, reversed the decrease of p-AKT expression and increased the expression of p-JNKs and p-c-Jun elicited by I/R injury. In addition, PHLPP2 inhibition reversed I/R-injury-induced Caspase-3 cleavage and loss of pyramid neurons in the CA1 region of hippocampus. The results of the current study indicate that the assembly of the FKBP51-PHLPP2-AKT signaling complex plays a critical role in mediating cell death in I/R injury. The inhibition of PHLPP2 via antisense oligonucleotide treatment may be an effective method to prohibit the assembly of the FKBP51-PHLPP-AKT signaling complex, thus balancing the cell pro-survival and pro-death signaling pathways ultimately mitigating cell death in I/R injury.
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PMID:Assembly of the FKBP51-PHLPP2-AKT signaling complex in cerebral ischemia/reperfusion injury in rats. 2474 96

Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.
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PMID:Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation. 2755 6