Verdugo-Sivianes, Eva M.Carnero, Amancio2022-11-072022-11-072021-05-06Verdugo-Sivianes EM, Carnero A. Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle. Cancers. 2021 May 6;13(9):2226http://hdl.handle.net/10668/4331Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/RB family proteinsPocket proteinsCell cyclePhosphatase PP1SpinophilinPPP1R9BCancerTumorigenesisRetinoblastoma proteinPhosphorylationCatalytic subunitCyclin-dependent kinasesStem cellBreast cancerHoloenzymesProteína fosfatasa 1NeoplasiasCarcinogénesisProteína de retinoblastomaFosforilaciónDominio catalíticoQuinasas ciclina-dependientesCélulas madreNeoplasias de la mamaHoloenzimasMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Retinoblastoma ProteinMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Phosphoprotein Phosphatases::Protein Phosphatase 1Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::PhosphorylationMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites::Catalytic DomainMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Substrate SpecificityMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Cyclin-Dependent KinasesMedical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem CellsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::CarcinogenesisMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::HoloenzymesMedical Subject Headings::Anatomy::Respiratory System::LungMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Interphase::G1 Phasereview article34066428open access10.3390/cancers130922262072-6694PMC8124259