Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3: implications for the control of protein stability and PTEN-protein interactions - PubMed (original) (raw)
. 2003 Aug 15;278(33):30652-60.
doi: 10.1074/jbc.M212610200. Epub 2003 Jun 3.
Affiliations
- PMID: 12788938
- DOI: 10.1074/jbc.M212610200
Free article
Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3: implications for the control of protein stability and PTEN-protein interactions
Josema Torres et al. J Biol Chem. 2003.
Free article
Abstract
PTEN phosphatase is one of the most commonly targeted tumor suppressors in human cancers and a key regulator of cell growth and apoptosis. We have found that PTEN is cleaved by caspase-3 at several target sites, located in unstructured regions within the C terminus of the molecule. Cleavage of PTEN was increased upon TNFalpha-cell treatment and was negatively regulated by phosphorylation of the C-terminal tail of PTEN by the protein kinase CK2. The proteolytic PTEN fragments displayed reduced protein stability, and their capability to interact with the PTEN interacting scaffolding protein S-SCAM/MAGI-2 was lost. Interestingly, S-SCAM/MAGI-2 was also cleaved by caspase-3. Our findings suggest the existence of a regulatory mechanism of protein stability and PTEN-protein interactions during apoptosis, executed by caspase-3 in a PTEN phosphorylation-regulated manner.
Similar articles
- Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases.
Valiente M, Andrés-Pons A, Gomar B, Torres J, Gil A, Tapparel C, Antonarakis SE, Pulido R. Valiente M, et al. J Biol Chem. 2005 Aug 12;280(32):28936-43. doi: 10.1074/jbc.M504761200. Epub 2005 Jun 10. J Biol Chem. 2005. PMID: 15951562 - Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.
Tolkacheva T, Boddapati M, Sanfiz A, Tsuchida K, Kimmelman AC, Chan AM. Tolkacheva T, et al. Cancer Res. 2001 Jul 1;61(13):4985-9. Cancer Res. 2001. PMID: 11431330 - Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex.
Vazquez F, Grossman SR, Takahashi Y, Rokas MV, Nakamura N, Sellers WR. Vazquez F, et al. J Biol Chem. 2001 Dec 28;276(52):48627-30. doi: 10.1074/jbc.C100556200. Epub 2001 Nov 13. J Biol Chem. 2001. PMID: 11707428 - Regulation of the PTEN phosphatase.
Gericke A, Munson M, Ross AH. Gericke A, et al. Gene. 2006 Jun 7;374:1-9. doi: 10.1016/j.gene.2006.02.024. Epub 2006 Mar 14. Gene. 2006. PMID: 16675164 Review. - PTEN: from pathology to biology.
Sulis ML, Parsons R. Sulis ML, et al. Trends Cell Biol. 2003 Sep;13(9):478-83. doi: 10.1016/s0962-8924(03)00175-2. Trends Cell Biol. 2003. PMID: 12946627 Review.
Cited by
- Cell-free DNA fragmentomics and second malignant neoplasm risk in patients with PTEN hamartoma tumor syndrome.
Liu D, Yehia L, Dhawan A, Ni Y, Eng C. Liu D, et al. Cell Rep Med. 2024 Feb 20;5(2):101384. doi: 10.1016/j.xcrm.2023.101384. Epub 2024 Jan 18. Cell Rep Med. 2024. PMID: 38242121 Free PMC article. - Mapping enzyme activity in living systems by real-time mid-infrared photothermal imaging of nitrile chameleons.
He H, Yin J, Li M, Dessai CVP, Yi M, Teng X, Zhang M, Li Y, Du Z, Xu B, Cheng JX. He H, et al. Nat Methods. 2024 Feb;21(2):342-352. doi: 10.1038/s41592-023-02137-x. Epub 2024 Jan 8. Nat Methods. 2024. PMID: 38191931 Free PMC article. - PINK1-PTEN axis promotes metastasis and chemoresistance in ovarian cancer via non-canonical pathway.
Zheng F, Zhong J, Chen K, Shi Y, Wang F, Wang S, Tang S, Yuan X, Shen Z, Tang S, Xia D, Wu Y, Lu W. Zheng F, et al. J Exp Clin Cancer Res. 2023 Nov 9;42(1):295. doi: 10.1186/s13046-023-02823-w. J Exp Clin Cancer Res. 2023. PMID: 37940999 Free PMC article. - Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants.
Torices L, Nunes-Xavier CE, López JI, Pulido R. Torices L, et al. PLoS One. 2023 Aug 1;18(8):e0289369. doi: 10.1371/journal.pone.0289369. eCollection 2023. PLoS One. 2023. PMID: 37527256 Free PMC article. - Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.
Langdon CG. Langdon CG. Biomolecules. 2023 Jan 30;13(2):259. doi: 10.3390/biom13020259. Biomolecules. 2023. PMID: 36830628 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials