title: Ubiquitin-specific protease 22 (USP22) positively regulates RCAN1 protein levels through RCAN1 de-ubiquitination.
abstract: Protein ubiquitination can be reversed by de-ubiquitinating enzymes (DUBs), which are classified into two main classes, cysteine proteases and metalloproteases. Cysteine proteases include ubiquitin-specific proteases (USPs) and ubiquitin C-terminal hydrolases. USP22 is a USP family member and a component of the mammalian Spt-Ada-Gcn5 acetyltransferase transcriptional coactivating complex. Regulator of calcineurin 1 (RCAN1; also known as DSCR1 or MCIP1) functions as an endogenous inhibitor of calcineurin signaling. In the present study, we have identified a novel interaction between USP22 and RCAN1 (RCAN1-1S) in the mammalian cells. In addition, the overexpression of USP22 caused the increase of RCAN1 protein stability. USP22 antagonized the actions of FBW7, NEDD4-2, and β-TrCP E3 ligase on RCAN1 and promoted RCAN1 de-ubiquitination. Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-α (IFN-α) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation. Taken together, these results suggest that USP22 positively regulates RCAN1 levels, which would consequently affect diverse RCAN1-linked cellular processes, such as the inflammatory process involving the release of IFN-α.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Ahyoung
authors.initials: A
authors.lastname: Hong
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D044767:Ubiquitin-Protein Ligases; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human