Molecular basis of inherited protein C deficiency results from genetic variations in the signal peptide and propeptide regions.

ABSTRACT:

Background

Inherited protein C deficiency (PCD) caused by mutations in protein C (PC) gene (PROC) increases the risk of thrombosis. Missense mutations in PC's signal peptide and propeptide have been reported in patients with PCD, but their pathogenic mechanisms, except mutations in R42 residue, remain unclear.

Objectives

To investigate the pathogenic mechanisms of inherited PCD caused by 11 naturally occurring missense mutations in PC's signal peptide and propeptide.

Methods

Using cell-based assays, we evaluated the impact of these mutations on various aspects such as activities and antigens of secreted PC, intracellular PC expression, subcellular localization of a reporter protein, and propeptide cleavage. Additionally, we investigated their effect on pre-messenger R

SUBMITTER: Cao Q 

PROVIDER: S-EPMC10592384 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature