Research Topics
Genomes and Genes
| Steven I ReedSummaryAffiliation: The Scripps Research Institute Country: USA Publications
Research Grants
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Detail Information
Publications
Coordinated spindle assembly and orientation requires Clb5p-dependent kinase in budding yeastM Segal
Department of Molecular Biology, MB7, The Scripps Research Institute, La Jolla, California 92037, USA
J Cell Biol 148:441-52. 2000..In contrast, B-type cyclins, Clb3p and Clb4p, though partially redundant with Clb5p for an early role in spindle morphogenesis, preferentially promote spindle assembly...- A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1S Jensen
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Cell Biol 152:27-40. 2001..Finally, mutational analysis reveals that the conserved COOH-terminal region of Esp1 is important for spindle interaction... 
The ubiquitin-proteasome pathway in cell cycle controlSteven I Reed
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Results Probl Cell Differ 42:147-81. 2006..Targeting of proteins for destruction by phosphorylation provides a mechanism for linking cell cycle regulation to internal and external signaling pathways via regulated protein kinase activities...- Cooperation between different Cdc4/Fbw7 isoforms may be associated with 2-step inactivation of SCF(Cdc4) targetsSteven I Reed
Department of Molecular Biology, MB 7, The Scripps Research Institute, La Jolla, California 92037, USA
Cell Cycle 5:1923-4. 2006..In this proposed model, targets of SCF(Cdc4) are first subjected to prolyl isomerization, creating a signal for translocation and sequestration in the nucleolus, where they are then multiubiquitylated... - Deregulation of cyclin E in human cells interferes with prereplication complex assemblySusanna Ekholm-Reed
Dept of Molecular Biology, MB 7, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
J Cell Biol 165:789-800. 2004..Cyclin E-mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation... - Mutation of hCDC4 leads to cell cycle deregulation of cyclin E in cancerSusanna Ekholm-Reed
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA
Cancer Res 64:795-800. 2004..These results indicate that hCdc4 function is an absolute prerequisite for cell cycle regulation of cyclin E levels, and loss of hCdc4 function is sufficient to deregulate cyclin E... - Ratchets and clocks: the cell cycle, ubiquitylation and protein turnoverSteven I Reed
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Rev Mol Cell Biol 4:855-64. 2003 
Deathproof: new insights on the role of skp2 in tumorigenesisSteven I Reed
Department of Molecular Biology, MB 7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Cancer Cell 13:88-9. 2008....- Keeping p27(Kip1) in the cytoplasm: a second front in cancer's war on p27Steven I Reed
Department of Molecular Biology, MB-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Cell Cycle 1:389-90. 2002 - Cell cycling? Check your brakesSteven I Reed
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Nat Cell Biol 4:E199-201. 2002..This is clearly the age of the negative cell cycle regulator, as a large percentage of the talks focused on the critical roles of cell cycle inhibitory networks... - Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cellsHanna Stina Martinsson-Ahlzén
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell Biol 28:5698-709. 2008.... - Phosphorylation of Mcm2 by Cdc7 promotes pre-replication complex assembly during cell-cycle re-entryLi Chiou Chuang
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell 35:206-16. 2009..These results are consistent with a role for cyclin E-Cdk2 in promoting the accumulation of Cdc6 and Cdc7, which is required for Mcm2 loading when cells re-enter the cell cycle from quiescence... - The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2)Donato Tedesco
Department of Molecular Biology, MB 7, The Scripps Research Institute, La Jolla, California 92037, USA
Genes Dev 16:2946-57. 2002..Thus, like the Cdk inhibitor p27(Kip1), p130 turnover is regulated by Cdk-dependent G1 phosphorylation leading to ubiquitin-dependent proteolysis... - Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoformsFrank van Drogen
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Mol Cell 23:37-48. 2006..Furthermore, in the context of Cdc4alpha and cyclin E, mutational data suggest that Pin1 isomerizes a noncanonical proline-proline bond, with the possibility that Cdc4alpha may serve as a cofactor for altering the specificity of Pin1... - A kinase-independent function of Cks1 and Cdk1 in regulation of transcriptionVeronica P C C Yu
Department of Molecular Biology, MB 7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell 17:145-51. 2005..However, it is independent of the protein kinase activity of Cdc28. In the absence of Cks1, neither Cdc28 nor the proteasome can be recruited. Consequently, there is a failure to maintain efficient transcription... - Cyclin E overexpression impairs progression through mitosis by inhibiting APC(Cdh1)Jamie M Keck
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
J Cell Biol 178:371-85. 2007..We further show that the accumulation of securin and cyclin B1 can account for the cyclin E-mediated mitotic phenotype... - Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteinsVasco Liberal
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 109:2754-9. 2012.... - SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysisBrian L Olson
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Genes Dev 22:252-64. 2008..These results suggest that attenuation of SCF(Cdc4)-dependent proteasomal degradation of PGC-1alpha has a role in mediating the PGC-1alpha-dependent transcriptional response to oxidative stress... - Cks1, Cdk1, and the 19S proteasome collaborate to regulate gene induction-dependent nucleosome eviction in yeastSusana Chaves
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell Biol 30:5284-94. 2010..These data suggest a model where binding of a complex consisting of Cks1, Cdk1, and the 19S proteasome to histone H4 leads to removal of nucleosomes via a nonproteolytic activity of the proteasome... - Improved identification of SUMO attachment sites using C-terminal SUMO mutants and tailored protease digestion strategiesJames A Wohlschlegel
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Proteome Res 5:761-70. 2006.... - The protease activity of yeast separase (esp1) is required for anaphase spindle elongation independently of its role in cleavage of cohesinChris Baskerville
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Genetics 178:2361-72. 2008..These data suggest that another protein, possibly a spindle-associated protein, is cleaved by Esp1 to allow anaphase. Such a function is consistent with the previous observation that Esp1 localizes to the mitotic spindle during anaphase... - S-phase checkpoint controls mitosis via an APC-independent Cdc20p functionDuncan J Clarke
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Cell Biol 5:928-35. 2003..Catastrophic mitosis induced by Cdc20p in S phase occurs even in the absence of core APC components. Thus, Cdc20p can function independently of the APC... - hCDC4 gene mutations in endometrial cancerCharles H Spruck
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Cancer Res 62:4535-9. 2002..Our results show that the hCDC4 gene is mutated in primary human tumors and suggest that it may function as a tumor suppressor in the genesis of many human cancers... - Reduced spermatogonial proliferation and decreased fertility in mice overexpressing cyclin E in spermatogoniaVasco Liberal
Department of Molecular Biology, MB 7, The Scripps Research Institute, La Jolla, CA
Cell Cycle 9:4222-7. 2010..Overall our results show that deregulation of cyclin E expression contribute to infertility, due to inability of the spermatogonial cells to start the mitotic cycles prior to entering meiosis... - Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeastMay C Morris
The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nature 423:1009-13. 2003.... - Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancerCharles Spruck
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Cancer Res 66:7355-60. 2006..Therefore, the detection of LMW derivatives of cyclin E1 is likely a function of cyclin E1 protein levels, and the activity of the proteolytic machinery responsible for their generation is not a tumor-specific property... - Kar9p-independent microtubule capture at Bud6p cortical sites primes spindle polarity before bud emergence in Saccharomyces cerevisiaeMarisa Segal
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Mol Biol Cell 13:4141-55. 2002..Finally, interactions away from Bud6p sites within the bud differ from those occurring at the mother cell cortex, pointing to the existence of an independent factor controlling cortical contacts in mother cells after bud emergence... - Cks1 is dispensable for survival in Saccharomyces cerevisiaeVeronica P C C Yu
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Cell Cycle 3:1402-4. 2004..In addition, we uncovered additional phenotypes (including a meiotic defect, sensitivity to high salt and inositol auxotrophy), all of which are defects associated with mutations in genes involved in general transcription pathways... - Requirement of Cks2 for the first metaphase/anaphase transition of mammalian meiosisCharles H Spruck
Department of Molecular Biology, MB 7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 300:647-50. 2003.... - Phosphorylation of the septin cdc3 in g1 by the cdc28 kinase is essential for efficient septin ring disassemblyCarol S L Tang
The Scripps Research Institute, Department of Molecular Biology, MB 7, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Cell Cycle 1:42-9. 2002..Thus, phosphorylation of Cdc3 by the Cdc28 kinase at the end of G1 may facilitate initiation of a new cell cycle by promoting disassembly of the obsolete septin ring from the previous cell cycle... - Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomesCurt Wittenberg
Department of Molecular Biology, MB-3, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Oncogene 24:2746-55. 2005..Such insights derived from analysis of specific genes when combined with genome-wide analysis provide a more detailed and integrated view of cell cycle-dependent transcription... - Improved flow cytometric analysis of the budding yeast cell cycleSteven B Haase
Department of Molecular Biology, MB7 The Scripps Research Institute La Jolla, California 92037, USA
Cell Cycle 1:132-6. 2002.... - Global analysis of protein sumoylation in Saccharomyces cerevisiaeJames A Wohlschlegel
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 279:45662-8. 2004..Additionally, our global analysis has revealed a number of interesting biological patterns in the list of SUMO targets including a clustering of sumoylation targets within macromolecular complexes... - Switching of melanocyte pigmentation associated with pituitary pars intermedia tumors in Rb+/- and p27-/- female mice with yellow pelageAdrian P L Smith
The Scripps Research Institute, Department ofMolecular Biology, MB-7, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Comp Med 53:75-80. 2003..The switch from phaeomelanin to eumelanin in the fur is most likely due to out-competition of the agouti gene product by alpha-melanocyte-stimulating hormone from the pituitary tumors, an effect masked in black or agouti mice... - Protein-protein interactions involved in the recognition of p27 by E3 ubiquitin ligaseKui Xu
Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Biochem J 371:957-64. 2003..Cks1 does not bind directly to the p27 phosphopeptide or to Skp1, which confirms its suggested role as an allosteric effector of Skp2... - Both SCF(Cdc4alpha) and SCF(Cdc4gamma) are required for cyclin E turnover in cell lines that do not overexpress cyclin EOlle Sangfelt
Cancer Center Karolinska, Karolinska sjukhuset, Department of Oncology Pathology, Stockholm, Sweden
Cell Cycle 7:1075-82. 2008..Under these circumstances, Cdc4alpha is sufficient for cyclin E turnover. Furthermore, the requirement for Cdc4gamma can be bypassed by ectopic overexpression of cyclin E... - Germline exclusion of Cks1 in the mouse reveals a metaphase I role for Cks proteins in male and female meiosisPeter J Donovan
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennslvania 19107, USA
Cell Cycle 2:275-6. 2003 - Cdc20 in S-phase: the Banquo at replication's banquetCatherine A Andrews
Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
Cell Cycle 3:276-9. 2004..Meanwhile, evidence has emerged suggesting that at least one of the specificity factors, Cdc20p, might be capable of functioning independently of the APC/C... - FBXW7/hCDC4 is a general tumor suppressor in human cancerShahab Akhoondi
Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
Cancer Res 67:9006-12. 2007..Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer... - Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6Leisa P Jackson
DCMB Group, Department of Biology, Box 91000, LSRC Bldg, Research Dr, Durham, NC 27708, USA
Mol Cell Biol 26:2456-66. 2006..Taken together, these findings suggest that the SCF(Cdc4) ubiquitin ligase complex regulates Clb6 turnover and that the functional differences exhibited by Clb5 and Clb6 arise from the distinct mechanisms controlling their stability... - Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesisUlrich B Keller
Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN, USA
EMBO J 26:2562-74. 2007..Therefore, Myc suppresses p27(Kip1) expression, accelerates cell proliferation and promotes tumorigenesis at least in part through its ability to selectively induce Cks1... - Differential contribution of Bud6p and Kar9p to microtubule capture and spindle orientation in S. cerevisiaeStephen M Huisman
Department of Genetics, University of Cambridge, Cambridge, CB2 3EH UK
J Cell Biol 167:231-44. 2004..Together, these results demonstrate Bud6p function in MT capture at the cell cortex, independent of Kar9p-mediated MT delivery along actin cables... - Cyclin E dysregulation and chromosomal instability in endometrial cancerMichael M Hubalek
Department of Obstetrics and Gynecology, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria
Oncogene 23:4187-92. 2004..These data suggest that impairment of cell cycle regulated proteolysis of cyclin E may be linked to carcinogenesis by promoting genomic instability...
Research Grants
- CONTROL OF CELL DIVISION IN YEASTSteven Reed; Fiscal Year: 2007..Ultimately, such information will be important for the diagnosis and treatment of human diseases such as cancer. ..
- The role of Cyclin E in growth control and tumorogenesisSteven Reed; Fiscal Year: 2007..It is hoped that these investigations will provide insights that will ultimately lead to improved prognosis and therapy. ..
- The role of Cdc4/Fbw7 in Parkinson's DiseaseSteven I Reed; Fiscal Year: 2010..The current proposal seeks to determine the function of parkin, encoded by the PARK2 gene, in the hope of developing new therapeutic approaches to Parkinson's disease. ..
- The role of Cyclin E in growth control and tumorogenesisSteven I Reed; Fiscal Year: 2010..In part, this is because many mechanistic questions concerning the basic biology of cancer remain unanswered. This proposal seeks to address some of these unanswered questions. ..
- THE S. CEREVISIAE S PHASE CHECKPOINTSteven Reed; Fiscal Year: 2003....
- CKS PROTEINS IN CELL CYCLE CONTROL AND TUMOROGENESISSteven Reed; Fiscal Year: 2001....
- CYCLIN E AND GROWTH CONTROL AND TUMOROGENESISSteven Reed; Fiscal Year: 2002..Because reagents and technology are already available for carrying out most of these studies, it is anticipated that rapid progress can be achieved on all research avenues proposed. ..
- CKS PROTEINS IN CELL CYCLE CONTROL AND TUMOROGENESISSteven I Reed; Fiscal Year: 2010..In part, this is because many mechanistic questions concerning the basic biology of cancer remain unanswered. This proposal seeks to address some of these unanswered questions. ..