A degradable form of polyoma small T antigen reveals the high specificity of TAZ in regulating gene expression

• 成果类型: Article
• 署名作者: Wang, Yubao; Manokaran, Cherubin; Huang, Kevin; Schaffhausen, Brian; Roberts, Thomas M.
• 署名单位: Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Tufts University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9633
• DOI: 10.1073/pnas.2426862122
• 发表日期: 2025-07-03
• 关键词: yes-associated protein; yap; domain; GROWTH; association; PATHWAY; middle; tead

摘要

The study of DNA tumor viruses has revolutionized cancer biology, partly by virtue of the unique capabilities of viral oncoproteins to manipulate key proteins and pathways involved in tumorigenesis. We find a high affinity and selective binding of the polyoma small T antigen (PyST) with the transcription cofactor TAZ. engineering a degradable version of PyST, we demonstrate that, when TAZ activity is modulated by PyST, a surprisingly small number of genes have altered expression and thus are candidate transcription targets of TAZ. Notably, knocking out TAZ, or its target genes CTGF or CYR61, abolishes the growth-promoting properties PyST that are evident upon growth factor withdrawal. Therefore, by controlling protein abundance of PyST and consequently TAZ activity, we find that TAZ is transcriptional coactivator that can achieve important biological effects by acting a limited number of gene targets.