Tripartite motif-containing protein 35 (TRIM35)

Tripartite motif-containing protein 35 (TRIM35) is an E3 ubiquitin-protein ligase and member of the TRIM family, characterized by a RING domain, two B-box domains, a coiled-coil region, and multiple zinc-finger motifs[1][4]. TRIM35 plays a multifunctional role in cellular biology, including regulating **protein ubiquitination** (notably of PKM2 and histone H2B), **cell death/apoptosis**, **glucose metabolism** (especially by suppressing the Warburg effect in cancer cells), and the **immune response**[1][2][3][4]. It acts as a tumor suppressor in hepatocellular carcinoma and breast cancer by inhibiting phosphorylation and modifying the oligomerization of PKM2, thereby suppressing tumor cell proliferation and metabolism[1][2]. In cardiac cells, TRIM35 mediates monoubiquitination of histone H2B (H2BK120Ub), facilitates p53-dependent transcription, and contributes to chromatin remodeling and potentially heart failure pathogenesis[3]. Low TRIM35 expression is associated with poorer prognosis in cancers, highlighting its potential as a **therapeutic target and biomarker** in oncology and cardiovascular disease[1][2][3].

Other names

HLS5MAIRE3 ubiquitin-protein ligase TRIM35hemopoietic lineage switch protein 5KIAA1098

Inhibition of pyruvate kinase M2 (PKM2) phosphorylation, curtailing the Warburg effect and tumor cell proliferation; Ubiquitination of histone 2B at lysine 120, leading to chromatin remodeling and increased p53-driven transcription in the heart; Regulation of PKM2 ubiquitination, altering its activity and metabolic phenotype in tumor cells; Stabilization of p53 protein levels