SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.

ABSTRACT: LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTB^M5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene-like functions to LACTB. Mechanistically, LACTB^M5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53^R156P protein from lysosomal degradation, whic

SUBMITTER: Huang G 

PROVIDER: S-EPMC11578386 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature