TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion.

ABSTRACT:

Background & aims

Molecular mechanisms underlying the different susceptibility of men and women to non-alcoholic fatty liver disease (NAFLD) are poorly understood. The TTC39B locus encodes a scaffolding protein, associates with gynecological disorders and its deletion protects mice from diet-induced steatohepatitis. This study aimed to elucidate the molecular mechanisms linking TTC39B (T39) to the expression of lipogenic genes and to explore sex-specific effects.

Methods

Co-expression in HEK293A cells validated the novel T39/pRb interaction predicted by a protein-protein interaction algorithm. T39 was knocked down using an antisense oligonucleotide (ASO) in mice with dietary NAFLD and a genetic deficiency of pRb or its downstream effector E2F1, as well as in primary human he

SUBMITTER: Hsieh J 

PROVIDER: S-EPMC8766887 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature