Zinc finger protein 36 homolog (ZFP36)

Zinc finger protein 36 homolog, widely known as Tristetraprolin (TTP), is a pivotal RNA-binding protein that serves as a major post-transcriptional regulator of the inflammatory response [1, 7]. It functions by binding to adenine-uridine-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) of various messenger RNAs, particularly those encoding pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-8 [1, 15]. Once bound, ZFP36 recruits the CCR4-NOT deadenylase complex to trigger the rapid degradation of these transcripts, effectively acting as a negative feedback 'brake' to limit inflammation [6, 13]. In the context of oncology, ZFP36 acts as a tumor suppressor by destabilizing the mRNAs of oncogenes like c-Myc and Cyclin D1; its expression is frequently downregulated in many invasive cancers [8, 14]. The activity of ZFP36 is tightly controlled by phosphorylation via the p38 MAPK/MK2 pathway, where phosphorylation by MK2 leads to its inactivation and sequestration by 14-3-3 proteins [13, 15]. Therapeutic strategies currently focus on indirect modulation, such as utilizing MK2 inhibitors or glucocorticoids to enhance ZFP36-mediated mRNA decay for the treatment of chronic inflammatory diseases and cancer [12, 22].

Other names

TristetraprolinTTPTIS11G0S24NUP475RNF162AZinc finger protein 36, C3H type, homolog

Promotes the degradation of mRNAs containing AU-rich elements (AREs) in their 3'-untranslated regions by recruiting the CCR4-NOT deadenylase complex, thereby limiting the production of pro-inflammatory cytokines and oncogenic proteins.