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

Zinc finger CCCH domain-containing protein 12A, commonly known as Regnase-1 or MCPIP1, is a critical endoribonuclease that functions as a key negative regulator of the inflammatory response. It acts by directly binding to and degrading the mRNAs of various pro-inflammatory cytokines, such as IL-6 and IL-12b, through its N-terminal PIN-like RNase domain and a CCCH-type zinc finger domain. This endogenous RNase pathway is essential for maintaining immune homeostasis; its absence or dysfunction leads to severe systemic autoimmune and inflammatory diseases characterized by the overproduction of cytokines. Beyond inflammation, ZC3H12A is involved in regulating angiogenesis, adipogenesis, and cell death pathways, making it a multifaceted player in cellular physiology. In the context of oncology, it can act as a tumor suppressor by limiting the expression of genes that promote cell proliferation and survival. While there are currently no approved drugs specifically targeting ZC3H12A, it is an area of intense research for treating chronic inflammatory conditions and certain cancers. Therapeutic strategies aim to either enhance its RNase activity to dampen inflammation or inhibit its degradation to stabilize its protective effects.

Other names

Regnase-1Monocyte chemotactic protein-induced protein 1MCPIP1MCP-induced protein 1

Degradation of pro-inflammatory mRNAs (e.g., IL-6, IL-12b) through its PIN-like ribonuclease domain to resolve inflammatory responses.