Zinc finger CCCH domain-containing protein 12A (ZC3H12A) (ZC3H12A)

Zinc finger CCCH domain-containing protein 12A (ZC3H12A), also known as Regnase-1, is a critical regulatory endoribonuclease that maintains immune homeostasis by degrading pro-inflammatory mRNAs (UniProt Q5D1E8). It specifically targets transcripts like IL-6, IL-12b, and c-Rel by recognizing conserved stem-loop structures in their 3' untranslated regions (Matsushita et al., 2009). In the context of disease, ZC3H12A acts as a potent brake on the inflammatory response; its deficiency is linked to severe autoimmune phenotypes and chronic inflammation (Iwasaki et al., 2011). Conversely, in oncology, Regnase-1 can limit the efficacy of T-cell-based therapies by dampening T-cell activation, making it a target for inhibition in CAR-T cell engineering to enhance anti-tumor immunity (Wei et al., 2019). While direct pharmacological modulators are still in early development, the protein's activity is naturally regulated by the protease MALT1, which cleaves and inactivates Regnase-1 upon immune stimulation (Jeltsch et al., 2014). Consequently, targeting the MALT1-Regnase-1 axis represents a promising therapeutic strategy for both inflammatory disorders and cancer (Mao et al., 2017).

Other names

Regnase-1Monocyte chemotactic protein-induced protein 1MCPIP1MCPIP

ZC3H12A acts as an endoribonuclease that recognizes and cleaves the 3' untranslated regions (UTRs) of specific pro-inflammatory mRNAs, such as IL-6 and IL-12b, thereby limiting the inflammatory response (Matsushita et al., 2009; UniProt Q5D1E8).