FBXO22 degrades nuclear PTEN to promote tumorigenesis.

Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN, here we ...
identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN. FBXO22 plays a tumor-promoting role by ubiquitylating and degrading nuclear PTEN. In accordance, FBXO22 is overexpressed in various cancer types, and contributes to nuclear PTEN downregulation in colorectal cancer tissues. Cumulatively, our study reports the mechanism to specifically regulate the stability of nuclear PTEN, which would provide the opportunity for developing therapeutic strategies aiming to achieve complete reactivation of PTEN as a tumor suppressor.
Mesh Terms:
Animals, Carcinogenesis, Cell Line, Tumor, Cell Nucleus, Cell Transformation, Neoplastic, Chromatography, Liquid, Colorectal Neoplasms, Cytoplasm, F-Box Proteins, Female, Humans, Mice, Mice, Inbred NOD, Mice, Nude, Mice, SCID, PTEN Phosphohydrolase, RNA, Small Interfering, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Tandem Mass Spectrometry, Tissue Array Analysis, Transplantation, Heterologous, Ubiquitination
Nat Commun
Date: Dec. 06, 2019
Download Curated Data For This Publication
226726
Switch View:
  • Interactions 59