|Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. |
Li, N; Zhang, Y; Han, X; Liang, K; Wang, J; Feng, L; Wang, W; Songyang, Z; Lin, C; Yang, L; Yu, Y; Chen, J
Genes & development
PTEN [phosphatidylinositol (3,4,5)-trisphosphate phosphatase and tensin homolog deleted from chromosome 10], a phosphatase and critical tumor suppressor, is regulated by numerous post-translational modifications, including phosphorylation, ubiquitination, acetylation, and SUMOylation, which affect PTEN localization and protein stability. Here we report ADP-ribosylation as a new post-translational modification of PTEN. We identified PTEN as a novel substrate of tankyrases, which are members of the poly(ADP-ribose) polymerases (PARPs). We showed that tankyrases interact with and ribosylate PTEN, which promotes the recognition of PTEN by a PAR-binding E3 ubiquitin ligase, RNF146, leading to PTEN ubiquitination and degradation. Double knockdown of tankyrase1/2 stabilized PTEN, resulting in the subsequent down-regulation of AKT phosphorylation and thus suppressed cell proliferation and glycolysis in vitro and tumor growth in vivo. Furthermore, tankyrases were up-regulated and negatively correlated with PTEN expression in human colon carcinomas. Together, our study revealed a new regulation of PTEN and highlighted a role for tankyrases in the PTEN-AKT pathway that can be explored further for cancer treatment.
|SET protein accumulates in HNSCC and contributes to cell survival: Antioxidant defense, Akt phosphorylation and AVOs acidification. |
Andréia M Leopoldino,Cristiane H Squarize,Cristiana B Garcia,Luciana O Almeida,Cezar R Pestana,Lays M Sobral,Sérgio A Uyemura,Eloiza H Tajara,J Silvio Gutkind,Carlos Curti
Determination of the SET protein levels in head and neck squamous cell carcinoma (HNSCC) tissue samples and the SET role in cell survival and response to oxidative stress in HNSCC cell lineages.
|Different cleavage pattern for poly(ADP-ribose) polymerase during necrosis and apoptosis in HL-60 cells. |
Shah, G M, et al.
Biochem. Biophys. Res. Commun., 229: 838-44 (1996)
Human promyelomonocytic leukemia cells HL-60 were treated with etoposide or cytochalasin B to induce apoptosis or necrosis, respectively. We report here that during necrosis, the DNA-repair associated nuclear enzyme poly(ADP-ribose) polymerase (PARP) was degraded differently from that observed during apoptosis. While apoptotic HL-60 cells exhibit only the signature 89 kDa fragment of PARP, necrosis of these cells was accompanied by formation of major fragments at MWr approximately 89 and 50 kDa and minor fragments at approximately 40 and 35 kDa. The necrosis-specific degradation of PARP was coincident with other changes detected by flow cytometric analysis, but earlier than the extensive degradation of DNA. Therefore, the unique necrotic degradation of PARP could be used as a sensitive indicator for necrotic death of cells.