IndraLab
Statements
sparser
"A speculative model might be that in response to DNA damage, phosphorylation of USP28 might activate it to deubiquitinate either GATA4 or an associated factor, thereby preventing its recognition by p62 and autophagic degradation, leading to GATA4 stabilization and SASP activation."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
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