2. Academic Validation
  3. Lysine long-chain fatty acylation regulates the TEAD transcription factor

Lysine long-chain fatty acylation regulates the TEAD transcription factor

  • Cell Rep. 2023 Apr 12;112388. doi: 10.1016/j.celrep.2023.112388.
Kota Noritsugu 1,  Takehiro Suzuki 2,  Kosuke Dodo 3,  Kenji Ohgane 4,  Yasue Ichikawa 5,  Kota Koike 4,  Satoshi Morita 6,  Takashi Umehara 6,  Kenji Ogawa 7,  Mikiko Sodeoka 3,  Naoshi Dohmae 2,  Minoru Yoshida 8,  Akihiro Ito 9
Affiliations

Affiliations

  • 1 School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan.
  • 2 Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 3 Synthetic Organic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Catalysis and Integrated Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 4 Synthetic Organic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 5 Drug Discovery Seed Compounds Exploratory Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 6 Laboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • 7 Drug Discovery Seed Compounds Exploratory Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; College of Bioresource Sciences, Nihon University, 1866, Kameino, Fujisawa-shi, Kanagawa 252-8510, Japan.
  • 8 Drug Discovery Seed Compounds Exploratory Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Department of Biotechnology, Graduate School of Agricultural Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Electronic address: yoshidam@riken.jp.
  • 9 School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan; Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: aito@toyaku.ac.jp.
PMID: 37060904 DOI: 10.1016/j.celrep.2023.112388
Abstract

TEAD transcription factors are responsible for the transcriptional output of Hippo signaling. TEAD activity is primarily regulated by phosphorylation of its coactivators, YAP and TAZ. In addition, cysteine palmitoylation has recently been shown to regulate TEAD activity. Here, we report lysine long-chain fatty acylation as a posttranslational modification of TEADs. Lysine fatty acylation occurs spontaneously via intramolecular transfer of acyl groups from the proximal acylated cysteine residue. Lysine fatty acylation, like cysteine palmitoylation, contributes to the transcriptional activity of TEADs by enhancing the interaction with YAP and TAZ, but it is more stable than cysteine acylation, suggesting that the lysine fatty-acylated TEAD acts as a "stable active form." Significantly, lysine fatty acylation of TEAD increased upon Hippo signaling activation despite a decrease in cysteine acylation. Our results provide insight into the role of fatty-acyl modifications in the regulation of TEAD activity.

Keywords

CP: Cell biology; Hippo pathway; TEAD; cysteine palmitoylation; lysine long-chain fatty acylation; transcription factor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-138565
    99.27%, YAP1/TAZ-TEAD Inhibitor
    YAP