Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving transferase
Reexamination Certificate
2011-04-26
2011-04-26
Long, Scott (Department: 1633)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving transferase
C435S007100
Reexamination Certificate
active
07932049
ABSTRACT:
The present invention is based at least in part on the discovery of a role for the JNK signaling pathway in longevity. In particular, the present inventors have shown that overexpression of c-jun N-terminal kinase 1 (jnk-1) extends lifespan and that said extended lifespan is associated with DAF-16 phosphorylation by JNK-1 and the consequent DAF-16 localization to the nucleus. Accordingly, the present invention features methods of identifying modulators of longevity in assays featuring organisms and/or cells having a JNK signaling pathway and, optionally, an IR signaling pathway. Also featured is an in vitro method of identifying an agent capable of enhancing longevity featuring an assay composition having a JNK signaling pathway molecule and insulin signaling pathway molecule. Further featured are therapeutic methods for the use of JNK signaling pathway modulators to enhance longevity, to prevent or reduce obesity and to prevent or treat type II diabetes.
REFERENCES:
patent: 7232897 (2007-06-01), Hotamisligil
patent: WO01/18549 (2001-03-01), None
Ip et al. Current Opinion in Cell Biology. 1998; 10:205-219.
Isobe. Current Genomics, 2000, vol. 1, No. 1. pp. 1-10.
Finkel et al. (Nature, Nov. 2000; 408: 239-247).
Driver (J. Amer. Aging Assoc., 2001; 24: 173-177).
Datta et al. (Genes & Development. 1999; 13: 2905-2927).
Al-Regaiey, Khalid A. et al., “Long-Lived Growth Hormone Receptor Knockout Mice: Interaction of Reduced Insulin-Like Growth Factor I/Insulin Signaling and Caloric Restriction,”Endocrinology, vol. 146(2):851-860 (2005).
Barbieri, Michelangela et al., “Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans,”Am. J. Physiol. Endocrinol. Metab., vol. 285:E1064-E1071 (2003).
Blüher, Matthias et al., “Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue,”Science, vol. 299:572-574 (2003).
Driver, Christopher, “An Hypothesis Concerning Control Networks and Aging in Drosophila Melanogaster and Caenorhabditis Elegans,”J. Amer. Aging Assoc., vol. 24:173-178 (2001).
Klöting, Nora et al., “Extended longevity and insulin signaling in adipose tissue,”Experimental Gerontology, vol. 40:878-883 (2005).
Wang, Meng C. et al., “JNK Signaling Confers Tolerance to Oxidative Stress and Extends Lifespan in Drosophila,”Developmental Cell, vol. 5:811-816 (2003).
Aguirre, Vincent et al, “The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307,”The Journal of Biological Chemistry, vol. 275(12):9047-9054 (2000).
Apfeld, Javier et al, “Cell Nonautonomy ofC. elegansdaf-2 Function in the Regulation of Diapause and Life Span,”Cell, vol. 95:199-210 (1998).
Barsyte, Dalia et al, “Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants ofCaenorhabditis elegans,”FASEB J., vol. 15:627-634 (2001).
Byrd, Dana Thyra et al, “UNC-16, a JNK-Signaling Scaffold Protein, Regulates Vesicle Transport inC. elegans,”Neuron, vol. 32:787-800 (2001).
Cavigelli, Martin et al, “Induction ofc-fosexpression through JNK-mediated TCF/Elk-1 phosphorylation,”The EMBO Journal, vol. 14(23):5957-5964 (1995).
Clancy, David J. et al, “Extension of Life-Span by Loss of CHICO, aDrosophilaInsulin Receptor Substrate Protein,”Science, vol. 292:104-106 (2001).
Dérijard, Benoit et al, “Independent Human MAP Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms,”Science, vol. 267:682-685 (1995).
Dlakić, Mensur, “A new family of putative insulin receptor-like proteins inC. elegans,”Curr. Biol., vol. 12(5):R155-R157 (2002).
Feng, Jinliu et al, “Mitochondrial Electron Transport Is a Key Determinant of Life Span in Caenorhabditis elegans,”Developmental Cell, vol. 1:633-644 (2001).
Friedman, David B. et al, “A Mutation in the age-1 Gene inCaenorhabditis elegansLengthens Life and Reduces Hermaphrodite Fertility,”Genetics, vol. 118:75-86 (1988).
Gems, David et al, “Two Pleiotropic Classes of daf-2 Mutation Affect Larval Arrest, Adult Behavior, Reproduction and Longevity inCaenorhabditis elegans,”Genetics, vol. 150:129-155 (1998).
Gerisch, Birgit et al, “A Hormonal Signaling Pathway InfluencingC. elegansMetabolism, Reproductive Development, and Life Span,”Developmental Cell, vol. 1:841-851 (2001).
Gil, Elad B. et al, “Regulation of the insulin-like developmental pathways ofCaenorhabditis elegansby a homolog of the PTEN tumor suppressor gene,”Proc. Natl. Acad. Sci.USA, vol. 96:2925-2930 (1999).
Hirosumi, J. et al, “A central role for JNK in obesity and insulin resistance,”Nature, vol. 420(6913):333-336 (2002).
Holzenberger, M. et al, “IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice,”Nature, vol. 421(6919):182-187 (2003).
Honda, Yoko et al, “The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression inCaenorhabditis elegans,”FASEB J., vol. 13:1385-1393 (1999).
Jia, Kailiang et al, “DAF-9, a cytochrome P450 regulatingC. eleganslarval development and adult longevity,”Development, vol. 129:221-231 (2002).
Kawasaki, Masato et al, “ACaenorhabditis elegansJNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons,”The EMBO Journal, vol. 18(13):3604-3615 (1999).
Kenyon, Cynthia, “Environmental Factors and Gene Activities That Influence Life Span,”C. Elegans II, Cold Spring Harbor Laboratory Press, Riddle, Donald L. et al, eds., Ch. 28 (1997).
Kido, Yoshiaki et al, “The Insulin Receptor and Its Cellular Targets,”The Journal of Clinical Endocrinology & Metabolism, vol. 86(3):972-979 (2001).
Kimura, K.D. et al, “daf-2, an insulin receptor-like gene that regulates longevity and diapause inCaenorhabditis elegans,”Science, vol. 277(5328):942-946 (1997).
Koga, Makoto et al, “ACaenorhabditis elegansMAP kinase kinase MEK-1, is involved in stress responses,”The EMBO Journal, vol. 19(19):5148-5156 (2000).
Lithgow, G.J. et al, “Stress resistance as a determinate ofC. eleganslifespan,”Mech. Ageing Dev., vol. 123(7):765-771 (2002).
Lithgow, G.J. et al, “Thermotolerance of a long-lived mutant ofCaenorhabditis elegans,”J. Gerontol., vol. 49(6):B270-B276 (1994).
Lithgow, Gordon J. et al, “Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress,”Proc. Natl. Acad. Sci.USA, vol. 92:7540-7544 (1995).
Maehama, Tomohiko et al, “The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate,”The Journal of Biological Chemistry, vol. 273(22):13375-13378 (1998).
Mihaylova, Valia T. et al, “The PTEN tumor suppressor homolog inCaenorhabditis elegansregulates longevity and dauer formation in an insulin receptor-like signaling pathway,”Proc. Natl. Acad. Sci.USA, Vol. 96:7427-7432 (1999).
Morris, Jason Z. et al, “A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause inCaenorhabditis elegans,”Nature, vol. 382:536-539 (1996).
Murakami, Shin et al, “A Genetic Pathway Conferring Life Extension and Resistance to UV Stress inCaenorhabditis elegans,”Genetics, vol. 143:1207-1218 (1996).
Ogg, Scott et al, “The C. elegans PTEN Homolog, DAF-18, Acts in the Insulin Receptor-like Metabolic Signaling Pathway,”Molecular Cell, vol. 2:887-893 (1998).
Paradis, Suzanne et al, “A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause inCaenorhabditis elegans,”Genes&Development, vol. 13:1438-1452 (1999).
Paradis, Suzanne et al, “Caenorhabditis elegansAkt/PKB transduces
Oh Seung Wook
Tissenbaum Heidi A.
Kanik Cynthia L.
Long Scott
Milasincic Esq. Debra J.
Nelson Mullins Riley & Scarborough LLP
University of Massachusetts
LandOfFree
Methods of identifying longevity modulators and therapeutic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods of identifying longevity modulators and therapeutic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of identifying longevity modulators and therapeutic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2719076