S100A8/S100A9 Cytokine Acts As a Transcriptional Coactivator During Breast Cellular Transformation

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Feb 1

PMID 33523865

Citations 24

Authors

Ruisheng Song

Kevin Struhl

Affiliations

Soon will be listed here.

Abstract

Cytokines are extracellular proteins that convey messages between cells by interacting with cognate receptors at the cell surface and triggering signaling pathways that alter gene expression and other phenotypes in an autocrine or paracrine manner. Here, we show that the calcium-dependent cytokines S100A8 and S100A9 are recruited to numerous promoters and enhancers in a model of breast cellular transformation. This recruitment is associated with multiple DNA sequence motifs recognized by DNA binding transcription factors that are linked to transcriptional activation and are important for transformation. The cytokines interact with these transcription factors in nuclear extracts, and they activate transcription when artificially recruited to a target promoter. Nuclear-specific expression of S100A8/A9 promotes oncogenic transcription and leads to enhanced breast transformation phenotype. These results suggest that, in addition to its classical cytokine function, S100A8/A9 can act as a transcriptional coactivator.

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