title: Protein tyrosine phosphatases PTP-1B, SHP-2, and PTEN facilitate Rb/E2F-associated apoptotic signaling.
abstract: To maintain tissue homeostasis, apoptosis is functionally linked to the cell cycle through the retinoblastoma (Rb)/E2F pathway. When the Rb tumor suppressor protein is functionally inactivated, E2F1 elicits an apoptotic response through both intrinsic (caspase-9 mediated) and extrinsic (caspase-8 mediated) apoptotic pathways in order to eliminate hyperproliferative cells. Rb/E2F-associated apoptosis has been demonstrated to be associated with the loss of constitutive transcriptional repression by Rb/E2F complexes and mediated by caspase-8. Protein tyrosine phosphatases (PTPs) PTP-1B and SHP-2 have been previously shown to be directly activated by loss of Rb/E2F repression during Rb/E2F-associated apoptosis. In this current study, we demonstrate that the PTEN tumor suppressor is also directly activated by loss of Rb/E2F repression. We also demonstrate that PTP-1B, SHP-2, and PTEN play a functional role in Rb/E2F-associated apoptosis. Knockdown of PTP1B, SHP2, or PTEN expression with small interfering RNA (siRNA) in apoptotic cells increases cell viability and rescues cells from the Rb/E2F-associated apoptotic response. Furthermore, rescue from apoptosis coincides with inhibition of caspase-8 and caspase-3 cleavage (activation). Our results indicate PTP-1B, SHP-2, and PTEN all play a functional role in Rb/E2F-associated apoptotic signal transduction and provide further evidence that PTP-1B, SHP-2, and PTEN can contribute to tumor suppression through an Rb/E2F-associated mechanism.
authors.affiliation: Edinburg Regional Academic Health Center, Medical Research Division, University of Texas Health Science Center at San Antonio, Edinburg, Texas, United States of America.
authors.forename: Liza D
authors.initials: LD
authors.lastname: Morales
authors.affiliation: Department of Biology, University of Texas-Pan American, Edinburg, Texas, United States of America.
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Casillas Pavón
authors.affiliation: Edinburg Regional Academic Health Center, Medical Research Division, University of Texas Health Science Center at San Antonio, Edinburg, Texas, United States of America.
authors.forename: Jun Wan
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of Biology, University of Texas-Pan American, Edinburg, Texas, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Department of Biology, University of Texas-Pan American, Edinburg, Texas, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Capetillo
authors.affiliation: Edinburg Regional Academic Health Center, Medical Research Division, University of Texas Health Science Center at San Antonio, Edinburg, Texas, United States of America; Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Dae Joon
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Biology, University of Texas-Pan American, Edinburg, Texas, United States of America; Department of Biology, South Texas College, McAllen, Texas, United States of America.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lieman
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D050684:E2F Transcription Factors / Q000378:metabolism*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D059748:Proteolysis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; C516724:PTPN11 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020169:Caspases