Table 2.
Ubiquitinases and deubiquitinases of RIPK1 and its effect.
| Type of RIPK1 Regulation | Regulatory Enzyme (Gene Name) | Alteration | Effect | Ref. |
|---|---|---|---|---|
| Ubiquitination: K63, M1 | cIAPs (BIRCs) | Increased expression | Inflammatory bowel disease, rheumatoid arthritis | (49, 50) |
| Ubiquitination: M1 | HOIL-1 (RBCK-1) | Site mutation | Premature immunodeficiency, autoimmune disease, inability to synthesize the LUBAC complex | (52, 67) |
| Ubiquitination: M1 | SHARPIN (SHARPIN) | Inactivating mutation | TNF-dependent multiorgan inflammation, skin inflammation | (53, 55) |
| Deubiquitination: K63 | A20 (TNFAIP) | Loss of function in heterozygotes (HA20) | Behcet’s disease, juvenile idiopathic arthritis or rheumatoid arthritis, periodic fever with aphthous pharyngitis and adenitis, autoimmune thyroiditis, Crohn’s disease, SLE, and adult Stills disease with cardiovascular symptoms, nephrotic syndrome, vasculitis, respiratory tract infection | (60, 61) |
| Deubiquitination: K63, M1 | CYLD (CYLD) | Gene mutation | Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepitheliomas | (62) |
| Deubiquitination: M1 | OTULIN | Functional defects | Autoinflammation, panniculitis, and dermatologic syndrome (AIPDS) | (64, 68) |