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
Affiliations
Ava M. Boston
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
Abdulrahman M. Dwead
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
Marwah M. Al-Mathkour
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
Kezhan Khazaw
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
Jin Zou
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
Qiang Zhang
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
Guangdi Wang
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
Bekir Cinar
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; Corresponding author
Summary: 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.
