title: Functional definition of relevant epitopes on the tumor suppressor PTEN protein.
abstract: The binding of PTEN to PDZ-domain-containing proteins appears to play an important role in the control of cell growth, motility and apoptosis. In turn, this binding can be abrogated by cleavage of the PTEN C-terminal region by caspase-3. We have generated and characterized monoclonal antibodies (mAb) directed against distinct epitopes at the C-terminal region of PTEN, and used them to define protein-binding epitopes on PTEN and to study its cleavage by caspase-3. mAb directed against epitopes at the far C-terminus of PTEN blocked binding to PTEN cognate PDZ domains and did not recognize the caspase-3 cleaved PTEN fragments. On the other hand, mAb that recognized an epitope within the C2 domain of PTEN did not prevent binding to PDZ domains, but could detect the caspase-3 cleaved PTEN fragments. The analysis of PTEN cleavage by caspase-3 revealed that the lipid phosphatase activity of PTEN controls its own degradation by interfering with the PI3-K anti-apoptotic activity. Our results define protein-binding sites on the PTEN tumor suppressor at the immunochemical level, and suggest a regulatory link between PTEN phosphatase activity, caspase-3 sensitivity and PTEN-protein interactions.
authors.affiliation: Instituto de Investigaciones Citológicas/FVIB, Amadeo de Saboya 4, Valencia 46010, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Andrés-Pons
authors.forename: Miguel
authors.initials: M
authors.lastname: Valiente
authors.forename: Josema
authors.initials: J
authors.lastname: Torres
authors.forename: Anabel
authors.initials: A
authors.lastname: Gil
authors.forename: Isabel
authors.initials: I
authors.lastname: Roglá
authors.forename: Francisca
authors.initials: F
authors.lastname: Ripoll
authors.forename: Javier
authors.initials: J
authors.lastname: Cervera
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
mesh_terms: D001665:Binding Sites; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D000939:Epitopes; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000503:physiopathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D000939:Epitopes; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases