IndraLab
Statements
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"CK2-mediated phosphorylation of OTUB1 at S16 acts as a molecular switch that drives nuclear accumulation, which is essential for repairing ionizing radiation-induced DNA damage, independent of changes to its intrinsic catalytic activity. xref This phosphorylation pathway can be activated by cathepsin K inhibition (e.g., with odanacatib), leading to enhanced p53 stabilization and apoptosis sensitization. xref Conversely, phosphorylation at tyrosine 26 (Y26) by non-receptor tyrosine kinases (e.g., Src) induces distinct conformational changes that promote the specific stabilization of the mTORC1 component Raptor without affecting other substrates, demonstrating the high specificity of phosphorylation-mediated regulation. xref Additionally, the phosphorylated Y26 residue serves as a docking site for the cell cycle regulator p27, connecting OTUB1 to IFNγ-induced cell-cycle arrest. xref These mechanisms demonstrate how site-specific phosphorylation enables OTUB1 to process disparate upstream signals, such as DNA damage, and direct appropriate downstream responses."
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"Our findings show that the phosphorylation of OTUB1 at Ser 16 did not impact its catalytic activity and its ability to interact with K63-linked ubiquitin chains as well as the E2 enzyme, UBE2N. Instead, we demonstrated that Ser 16 phosphorylation of OTUB1 was essential for its nuclear accumulation, suggesting that nuclear roles of OTUB1 are likely to be regulated through CK2-mediated phosphorylation of OTUB1."