TY  - JOUR
AU  - He Yuan-ming
AU  - Zhou Xiu-min
AU  - Jiang Shuo-yi
AU  - Zhang Zu-bin
AU  - Cao Bi-yin
AU  - Liu Jin-bao
AU  - Zeng Yuan-ying
AU  - Zhao Jun
AU  - Mao Xin-liang
PY  - 2022
TI  - TRIM25 activates AKT/mTOR by inhibiting PTEN via K63-linked polyubiquitination in non-small cell lung cancer
JF  - Acta Pharmacologica Sinica; Vol 43, No 3 (March 2022): Acta Pharmacologica Sinica
Y2  - 2022
KW  - 
N2  - The PTEN/AKT/mTOR signaling pathway is frequently dysregulated in non-small cell lung cancer (NSCLC), but the mechanisms are not well-understood. The present study found that the ubiquitin ligase TRIM25 is highly expressed in NSCLC tissues and promotes NSCLC cell survival and tumor growth. Mechanistic studies revealed that TRIM25 binds to PTEN and mediates its K63-linked ubiquitination at K266. This modification prevents the plasma membrane translocation of PTEN and reduces its phosphatase activity therefore accumulating PI(3,4,5)P3. TRIM25 thus activates the AKT/mTOR signaling. Moreover, we found that the antibacterial nitroxoline can activate PTEN by reducing its K63-linked polyubiquitination and sensitizes NSCLC to cisplatin-induced apoptosis. This study thus identified a novel modulation on the PTEN signaling pathway by TRIM25 and provides a potential target for NSCLC treatment.
UR  - http://www.chinaphar.com/article/view/10509