IndraLab

"Accordingly, since TAK1 is required for JNK activation, leading to insulin resistance, and since USP18 inhibits TAK-1, an insulin-sensitizing effect of USP18 has been shown in the liver [ xref , xref ]."

"In a transverse aortic constriction (TAC) mouse model, USP18 is found to be associated with myocardial hypertrophy through TAK1/p38/JNK1/2 pathway, USP18 deficiency enhances TAK1 activity in response to pressure overload [73], whereas USP18 overexpression attenuates pathological cardiac remodeling [157]."

"Recent work has demonstrated that USP18 has the ability to deubiquitinate the transforming growth factor activated kinase 1 (TAK1) complexes required for NF-kappaB activation in T cells and that overexpression of USP18 leads to decreased nuclear activation and impaired formation of TAK1 complexes."

"USP18 was shown to inhibit the NFkappaB pathway and TAK1 ."

"The exacerbation of cardiac remodelling in mice with USP18 deficiency further confirmed the protective role of USP18 against cardiac dysfunction caused by pathological hypertrophy. xref A molecular study found that USP18 inactivates TAK1 by deubiquitinating K63‐linked polyubiquitination and it subsequently suppresses the downstream NF‐κB and JNK1/2 signalling pathways, which plays critical role in NAFLD progression. xref USP14 also contributes to suppress the development of cardiac hypertrophy by increasing phosphorylation of GSK‐3β (Table  xref ). xref Together, these findings indicate that the most of the DUBs protect the cardiac structure and function against pathological cardiac modelling caused by various stimulus."

"Accordingly , since TAK1 is required for JNK activation , leading to insulin resistance , and since USP18 inhibits TAK-1 , an insulin-sensitizing effect of USP18 has been shown in the liver [ 39 , 43 ] ."

"Furthermore, we demonstrated that USP18 can inhibit TAK1 activity by interfering with the K63 ubiquitination of TAK1."

"Mechanistically, USP18 inhibits TAK1 activation by removing the K63-linked ubiquitination chain."