SIK2 and hepatocellular carcinoma: Of note, p300-mediated acetylation inhibited ATP binding with and activating of SIK2 by disturbing its phosphorylation at Thr175, conversely, SIK2 can also directly phosphorylate and regulate p300 acetyltransferase.60 In addition, HDAC6 has been identified to activate SIK2 by removing its acetylation modification.9 In addition, RNF2, an E3 ligase, has been revealed to ubiquitinate and in turn degrade SIK1 in hepatoma cells.61 Consequently, the specific regulatory mechanisms of other PTMs to SIKs need to be further explored for fully understanding the upstream regulation for SIKs.