Monocyte chemotactic protein 1-induced protein 1 (MCPIP1) (MCPIP1)

Monocyte chemotactic protein 1-induced protein 1 (MCPIP1), also known as Regnase-1, is a critical regulatory protein that maintains immune homeostasis by controlling the stability of inflammatory mRNAs [1, 2]. It functions primarily as an endoribonuclease, specifically recognizing and cleaving the 3' untranslated regions (UTRs) of transcripts encoding pro-inflammatory cytokines such as IL-6, IL-12b, and IL-1b [2, 5]. Beyond its RNase activity, MCPIP1 possesses deubiquitinase activity, which allows it to negatively regulate the NF-kappaB and JNK signaling pathways by removing ubiquitin chains from signaling mediators like TRAF6 [3]. Its dysfunction is linked to various pathologies, including rheumatoid arthritis, psoriasis, and several types of cancer, where it often acts as a tumor suppressor by limiting chronic inflammation [4]. While no direct MCPIP1-targeted drugs are currently approved, indirect modulation via MALT1 inhibitors—which prevent the proteolytic cleavage and inactivation of MCPIP1—is an active area of pharmacological research [5]. Therapeutic strategies aiming to stabilize or enhance MCPIP1 activity hold promise for treating hyper-inflammatory conditions and certain malignancies.

Other names

Regnase-1ZC3H12AZinc finger CCCH domain-containing protein 12A

MCPIP1 acts as an endoribonuclease that degrades pro-inflammatory mRNAs by recognizing stem-loop structures in their 3' UTRs [2]. It also functions as a deubiquitinase, removing K63-linked ubiquitin chains from TRAF proteins to inhibit NF-kappaB signaling [3].