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)

The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner. Furthermore, this process was triggered via increase ubiquitination by the E3 ligase, Mule, rather than via de-ubiquitination by USP9X. Additionally, we found that Mcl-1 levels were only transiently reduced by KRIBB11: Mcl-1 levels were gradually restored as KRIBB11 activity diminished. However, we found that this effect was blocked in BIS (Bcl-2 interacting cell death suppressor, also called BAG3)-depleted cells, and that BIS prevents Mcl-1 from undergoing HSP70-driven proteasomal degradation, through an interaction with HSP70. Taken together, our results suggest that targeting Mcl-1 with KRIBB11 treatment, while simultaneously downregulating BIS, could be a therapeutic strategy in NSCLC.
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PMID:KRIBB11 accelerates Mcl-1 degradation through an HSF1-independent, Mule-dependent pathway in A549 non-small cell lung cancer cells. 2885 86

Thiram, a carbamate pesticide, is known to induce tibial dyschondroplasia (TD) in broiler chickens. This study used a thiram-induced TD model to explore whether apoptosis-related genes were expressed in erythrocytes of broiler chickens and the impacts of thiram-induced TD and the recombinant GSTA3 protein in regulating these genes expression. In this study, mRNA and protein expression of six types of apoptosis-related genes (Bcl-2, Bax, Murine double minute MDM2, Bcl-2-associated athanogene BAG-1, BAG-3, STAT3) were identified in erythrocytes of broiler chickens by real-time PCR and immunohistochemistry, and we also found that thiram-induced TD induced the decreased expression of these antiapoptotic genes in the initial stage of TD and promoted their expression in TD recovery, which suggested that the expression of these apoptosis-related genes in erythrocytes is highly related to the development of TD. Further, the recombinant GSTA3 protein promoted the expression of all apoptosis-related genes in the initial stage of TD and recovered the normal expression of these genes in the recovery stage of TD, which indicated that the recombinant GSTA3 protein may participate in the recovery of TD. Further studies are needed to elucidate the mechanism of the response of erythrocytes to thiram-induced TD and the recombinant protein GSTA3 in broiler chickens.
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PMID:Identification of apoptosis-related genes in erythrocytes of broiler chickens and their response to thiram-induced tibial dyschondroplasia and recombinant glutathione-S-transferase A3 protein. 3016 45


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