Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate

Ava M Boston; Abdulrahman M Dwead; Marwah M Al-Mathkour; Kezhan Khazaw; Jin Zou; Qiang Zhang; Guangdi Wang; Bekir Cinar

doi:10.1016/j.isci.2023.107964

Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate

iScience. 2023 Sep 20;26(10):107964. doi: 10.1016/j.isci.2023.107964. eCollection 2023 Oct 20.

Authors

Ava M Boston¹, Abdulrahman M Dwead¹, Marwah M Al-Mathkour¹, Kezhan Khazaw¹, Jin Zou¹, Qiang Zhang², Guangdi Wang², Bekir Cinar¹

Affiliations

¹ Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
² Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA.

Abstract

The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones.

Keywords: Cell biology; Molecular biology; Omics; Proteomics.

Abstract

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