If a particular compound is able to induce STAT3 degradation in SU-DHL-1(lymphoma) and K562(lymphoblast) cell lines but not in KG-1(bone-marrow) cell line, what may be the cause of it?
How is STAT3 regularly degraded (not inhibited- the band almost completely disappears along with p-STAT3 band)?
I'm assuming if the drug acts on an upstream target of STAT3 I would still see a band for STAT3 that was already existing in the cells prior to adding the test agent.
Any insights or comments would be helpful.
Dear Min!
Please You look at the article:
https://www.jbc.org/article/S0021-9258(20)45587-5/fulltext
Signal transducer and activator of transcription 3 (STAT3) regulated by calcineurin. Calcineurin promotes the degradation of STAT3 via the ubiquitin-proteasome pathway. Inhibition of calcineurin acutely increases total levels of STAT3 as well as its activated forms, resulting in decreased levels of the tumor suppressor p53 and its proapoptotic target, Bax. In vivo and in vitro, calcineurin regulates levels of STAT3 and neurotrophin dependence. TMF/ARA 160 (TATA element modulatory factor/androgen receptor co-activator 160), the key mediator of STAT3 ubiquitination, is required for calcineurin-dependent STAT3 degradation.
Most likely, the differences between different types of cells consist in the activation of various ubiquinty ligases, which ubiquinylate proteins, including STAT3, for their subsequent degradation by the proteosome.
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