This Week in PNAS

2005 Proceedings of the National Academy of Sciences of the United States of America  
2703 PTEN C-terminal domain suppresses transformation 3004 Illuminating genes in Vibrio 3093 CB 2 receptor activation inhibits pain via ␤-endorphin release 3111 Peripheral pathways of circadian rhythms 3135 Pathogen portals in plants and animals BIOCHEMISTRY PTEN C-terminal domain suppresses transformation According to Koichi Okumura et al., the C-terminal domain of the PTEN (phosphatase and tensin homologue) tumor suppressor protein inhibits transformation by the oncogenic MSP58 protein.
more » ... SP58 protein. Normally, PTEN suppresses tumorigenesis by down-regulating the PI3K pathway and p53 regulation via the phosphatase activity of its catalytic domain. However, the C-terminal region of PTEN, which helps to stabilize the protein, is mutated in a variety of human cancers, suggesting an additional mechanism by which PTEN regulates transformation. To elucidate the function of the PTEN C-terminal region, the authors used a yeast two-hybrid screen to identify PTEN-interacting proteins. The researchers found that the PTEN C-terminal domain physically interacts with the forkhead-associated (FHA) domain of the oncogenic MSP58 protein, and this interaction requires PTEN threonine 366. MSP58 transformed PTEN-deficient mouse embryonic fibroblasts, but reintroducing wild-type PTEN dramatically reduced the number of transformed foci. Furthermore, a PTEN mutant clone with an inactive catalytic domain (G129R) was still able to suppress MSP58 oncogenicity. These results demonstrate that the PTEN C-terminal region inhibits the transformational potential of MSP58, and this attenuation does not require PTEN catalytic activity. The authors propose that PTEN suppression of MSP58 transformation through protein-protein interactions represents a previously unidentified ability of PTEN to interfere with tumorigenesis. "Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor" by Koichi
doi:10.1073/iti0805102 fatcat:hjyiqyjevjcmlc2mjsbaippywi