Eloc-KO Mouse

Eloc, also known as TCEB1, encodes elongin C, a key component of the VCB-CR (pVHL, elongin C, elongin B, cullin 2 and ring box 1) E3 ubiquitin ligase complex. This complex is crucial in oxygen sensing and degradation of hypoxia-inducible factors, playing a significant role in multiple biological processes related to oxygen homeostasis [1,7].

A de novo pathogenic variant in ELOC (NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys)) was identified in a proband with von Hippel-Lindau (VHL) disease but without a detectable VHL mutation. This finding suggests that ELOC variants can be a novel cause for VHL disease [1]. Biallelic ELOC-inactivated renal cell carcinoma (RCC) is considered a novel subtype of renal cancer. ELOC-mutated RCC with biallelic ELOC inactivation shows distinct molecular features, such as no biallelic VHL and TSC1, TSC2, or mTOR inactivation, supporting it as a new, molecularly defined tumor entity [2]. ELOC-mutated RCC is also recognized as a novel molecularly-defined epithelial renal tumor in the 2022 WHO classification of urogenital tumours [3,4,6,8,9]. In colorectal cancer, USP51 binds to Elongin C and forms a complex with VHL E3 ligase to regulate the ubiquitin-dependent proteasomal degradation of HIF1A, promoting cancer stemness and chemoresistance [5].

In conclusion, Eloc is essential for the function of the VCB-CR E3 ubiquitin ligase complex, which is crucial for oxygen sensing. Research on Eloc-related genetic variants has revealed its potential role in diseases like VHL disease and in defining new subtypes of renal cell carcinoma. Understanding Eloc's function through model-based research can provide insights into the mechanisms of these diseases and potentially offer new therapeutic targets.