Acceleration of gastric tumorigenesis through MKRN1-mediated posttranslational regulation of p14ARF.

ABSTRACT:

Background

We investigated whether Makorin ring finger protein 1 (MKRN1), an E3 ligase, affects p14ARF-associated cellular senescence and tumorigenesis by posttranslational modification in gastric tumorigenesis.

Methods

A link between MKRN1 and ARF was examined in MKRN1 null mouse embryonic fibroblasts (MEFs) and in human fibroblasts and gastric cancer cells by silencing MKRN1 using small interfering RNA (siRNA) and short hairpin RNA (shRNA). Ubiquitination and proteasomal degradation assays were used to assess p14ARF degradation associated with MKRN1. MKRN1 and p14ARF expression levels were analyzed with immunohistochemistry in malignant and normal tissues from gastric cancer patients and with χ(2) tests. The tumor growth of gastric cancer cells stably expressing MKRN1 shRN

SUBMITTER: Ko A 

PROVIDER: S-EPMC3490844 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature