IndraLab

"Mechanistically, CK2-induced phosphorylation of USP4 is important for stabilization of SIRT1 by suppressing ubiquitin-dependent proteasomal degradation."

"The phosphorylation of USP4 by Ck2 can also inhibit the transcription of Sost by inhibiting ubiquitination degradation of SIRT1."

"Osteocytes are the main cells in mature bone tissue, accounting for about 95% of the total bone cells. xref Osteocytes can secrete paracrine factors, such as OPG, RANKL and sclerostin (Sost), which can participate in the regulation of osteoblast and osteoclast differentiation and activity and play a key role in bone remodelling. xref , xref Sost binds to LPR5/6 on osteoblast cell membranes to interfere with WNT binding to WNT receptor Frizzled, which acts as an antagonist of WNT/β‐catenin signalling to inhibit osteogenesis and bone formation. xref Sirtuin 1 (SIRT1) inhibits the expression of Sost by modifying the acetylation of H3K9 at the Sost promoter. xref , xref The phosphorylation of USP4 by casein kinase 2 (Ck2) inhibits the ubiquitination degradation of SIRT1, thus inhibiting the transcription of Sost and reducing the RANKL/OPG ratio in osteocytes, thereby reducing osteoclastogenesis and increasing osteoblastogenesis. xref Overall, Sost expression regulated by CK2–USP4–SIRT1 pathway is essential for osteocytes to maintain bone homeostasis."

"A study showed that casein kinase 2-induced phosphorylation of USP4 stabilizes sirtuin1 by inhibiting ubiquitin-dependent proteasomal degradation."