| Literature DB >> 31097636 |
Jonathan D Lee1,2, Jinfang Zhang3, Shu-Yu Lin4, Yu-Ru Lee1,2, Ming Chen1,2, Tian-Min Fu5,6, Hao Chen7,8, Tomoki Ishikawa1,2, Shang-Yin Chiang4,9, Jesse Katon1,2, Yang Zhang1,2, Yulia V Shulga1,2, Assaf C Bester1,2, Jacqueline Fung1,2, Emanuele Monteleone1,2,10, Lixin Wan3,11, Chen Shen5,6, Chih-Hung Hsu7,8,12, Antonella Papa13, John G Clohessy1,2,14, Julie Teruya-Feldstein15, Suresh Jain16, Hao Wu5,6, Lydia Matesic17, Ruey-Hwa Chen4,9, Wenyi Wei3, Pier Paolo Pandolfi18,2.
Abstract
Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain-containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.Entities:
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Year: 2019 PMID： 31097636 PMCID： PMC7081834 DOI： 10.1126/science.aau0159
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728