title: Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
abstract: Polycomb group (PcG) proteins are transcriptional repressors of genes involved in development and differentiation, and also maintain repression of key genes involved in the cell cycle, indirectly regulating cell proliferation. The human SCML2 gene, a mammalian homologue of the Drosophila PcG protein SCM, encodes two protein isoforms: SCML2A that is bound to chromatin and SCML2B that is predominantly nucleoplasmic. Here, we purified SCML2B and found that it forms a stable complex with CDK/CYCLIN/p21 and p27, enhancing the inhibitory effect of p21/p27. SCML2B participates in the G1/S checkpoint by stabilizing p21 and favoring its interaction with CDK2/CYCE, resulting in decreased kinase activity and inhibited progression through G1. In turn, CDK/CYCLIN complexes phosphorylate SCML2, and the interaction of SCML2B with CDK2 is regulated through the cell cycle. These findings highlight a direct crosstalk between the Polycomb system of cellular memory and the cell-cycle machinery in mammals.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, United States of America ; Spanish National Cancer Research Centre (CNIO), Molecular Oncology Programme, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Lecona
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Luis Alejandro
authors.initials: LA
authors.lastname: Rojas
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonasio
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Johnston
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Molecular Oncology Programme, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández-Capetillo
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D016213:Cyclins / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D063146:Polycomb-Group Proteins / Q000502:physiology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; C099357:SCM protein, Drosophila; C119751:SCML2 protein, human; D018844:Cyclin-Dependent Kinases