Tumor Antigen PRAME is a Potential Therapeutic Target of P53 Activation in Melanoma Cells

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2024 Jun 5

PMID 38835116

Authors

Yong-Kyu Lee

Hyeon Ho Heo

Nackhyoung Kim

Ui-Hyun Park

Hyesook Youn

Eun-Yi Moon

Eun-Joo Kim

Soo-Jong Um

Affiliations

Soon will be listed here.

Abstract

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activationmediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells. [BMB Reports 2024; 57(6): 299-304].

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