Tbc1d31-KO Mouse

Tbc1d31, a Rab GTPase activating protein, is involved in multiple biological processes. It assembles a complex at centrosomes with E3 ubiquitin ligase praja2, protein kinase A (PKA), and OFD1, playing a crucial role in primary ciliogenesis. This process links GPCR signalling to ubiquitylation and proteolysis of OFD1, which is important for cilium biology and development [1].

In hepatocellular carcinoma (HCC), genomic amplification of Tbc1d31 promotes tumour growth and metastasis. It reduces the Rab22A-mediated endolysosomal trafficking and degradation of EGFR, activating EGFR signalling. Additionally, ZSCAN16 can activate TBC1D31 transcriptionally, accelerating HCC progression [2,3]. A homozygous missense variant in Tbc1d31 has been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans [4]. In breast cancer, Tbc1d31 is among TBC1 domain-containing proteins expressed at higher levels in triple-negative breast cancers, correlating with elevated glycolytic metabolism [5].

In conclusion, Tbc1d31 is essential for primary ciliogenesis and is involved in multiple disease conditions such as HCC, CAKUT, and triple-negative breast cancer. Studies on Tbc1d31 contribute to understanding biological processes and disease mechanisms, potentially offering new therapeutic strategies for these diseases.