Biomaterial Database

Speedy/Ringo C regulates S and G2 phase progression in human cells. 2008

Aiyang Cheng, and Mark J Solomon

Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520-8024, USA.

Cyclin-dependent kinases (CDKs) control cell cycle transitions and progression. In addition to their activation via binding to cyclins, CDKs can be activated via binding to an unrelated class of cell cycle regulators termed Speedy/Ringo (S/R) proteins. Although mammals contain at least five distinct Speedy/Ringo homologues, the specific functions of members of this growing family of CDK activators remain largely unknown. We investigated the cell cycle roles of human Speedy/Ringo C in HEK293 cells. Down-regulation of Speedy/Ringo C by RNA interference delayed S and G(2) progression whereas ectopic expression had the opposite effect, reducing S and G(2)/M populations. Double thymidine arrest and release experiments showed that overexpression of Speedy/Ringo C promoted late S phase progression. Using a novel three-color FACS protocol to determine the length of G(2) phase, we found that the suppression of Speedy/Ringo C by RNAi prolonged G(2) phase by approximately 30 min whereas ectopic expression of Speedy/Ringo C shortened G(2) phase by approximately 25 min. In addition, overexpression of Speedy/Ringo C disrupted the G(2) DNA damage checkpoint, increased cell death and caused a cell cycle delay at the G(1)-to-S transition. These observations indicate that CDK-Speedy/Ringo C complexes positively regulate cell cycle progression during the late S and G(2) phases of the cell cycle.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D016195	G2 Phase	The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.	Gap Phase 2,Second Gap Phase,G2 Phases,Gap Phase, Second,Gap Phases, Second,Phase 2, Gap,Phase, G2,Phase, Second Gap,Phases, G2,Phases, Second Gap,Second Gap Phases
D016196	S Phase	Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.	S Period,Period, S,Periods, S,Phase, S,Phases, S,S Periods,S Phases
D016923	Cell Death	The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.	Death, Cell
D018797	Cell Cycle Proteins	Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.	Cell Division Cycle Proteins,Cell-Cycle Regulatory Proteins,cdc Proteins,Cell Cycle Regulatory Proteins
D018844	Cyclin-Dependent Kinases	Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.	Cyclin-Dependent Kinase,Cyclin-Dependent Protein Kinase,cdk Proteins,Cyclin-Dependent Protein Kinases,Cyclin Dependent Kinase,Cyclin Dependent Kinases,Cyclin Dependent Protein Kinase,Cyclin Dependent Protein Kinases,Kinase, Cyclin-Dependent,Kinase, Cyclin-Dependent Protein,Protein Kinase, Cyclin-Dependent
D034622	RNA Interference	A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.	Gene Silencing, Post-Transcriptional,Post-Transcriptional Gene Silencing,Co-Suppression,Cosuppression,Posttranscriptional Gene Silencing,RNA Silencing,RNAi,Co Suppression,Gene Silencing, Post Transcriptional,Gene Silencing, Posttranscriptional,Gene Silencings, Posttranscriptional,Interference, RNA,Post Transcriptional Gene Silencing,Post-Transcriptional Gene Silencings,Silencing, Post-Transcriptional Gene