SERGE FUCHS

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis
    K G Suresh Kumar
    Department of Animal Biology and 2Mari Lowe Center for Comparative Oncology Research, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 179:935-50. 2007
  2. pmc Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury
    Sabyasachi Bhattacharya
    Department of Animal Biology, School of Veterinary Medicine University of Pennsylvania, Philadelphia, PA, USA
    EMBO Mol Med 6:384-97. 2014
  3. pmc Inflammatory signaling compromises cell responses to interferon alpha
    W C Huangfu
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Oncogene 31:161-72. 2012
  4. pmc Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1
    Juan Qian
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 7:e1002065. 2011
  5. pmc Hope and fear for interferon: the receptor-centric outlook on the future of interferon therapy
    Serge Y Fuchs
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    J Interferon Cytokine Res 33:211-25. 2013
  6. pmc Ubiquitination-mediated regulation of interferon responses
    Serge Y Fuchs
    Department of Animal Biology and Mari Lowe Comparative Oncology Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    Growth Factors 30:141-8. 2012
  7. ncbi request reprint De-regulation of ubiquitin-dependent proteolysis and the pathogenesis of malignant melanoma
    Serge Y Fuchs
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA
    Cancer Metastasis Rev 24:329-38. 2005
  8. ncbi request reprint Tumor suppressor activities of the Fbw7 E3 ubiquitin ligase receptor
    Serge Y Fuchs
    Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104 6046, USA
    Cancer Biol Ther 4:506-8. 2005
  9. doi request reprint MYC-induced sensitivity of human malignant melanoma to proteasome inhibitors - a KaMYCaze effect
    Serge Y Fuchs
    Pigment Cell Melanoma Res 21:9-10. 2008
  10. pmc Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2
    Hui Zheng
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    Mol Cell Biol 31:710-20. 2011

Research Grants

Collaborators

Detail Information

Publications39

  1. pmc Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis
    K G Suresh Kumar
    Department of Animal Biology and 2Mari Lowe Center for Comparative Oncology Research, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 179:935-50. 2007
    ....
  2. pmc Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury
    Sabyasachi Bhattacharya
    Department of Animal Biology, School of Veterinary Medicine University of Pennsylvania, Philadelphia, PA, USA
    EMBO Mol Med 6:384-97. 2014
    ..These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. ..
  3. pmc Inflammatory signaling compromises cell responses to interferon alpha
    W C Huangfu
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Oncogene 31:161-72. 2012
    ..The roles of inflammation and p38 protein kinase in regulating cellular responses to IFNα/β in normal and tumor cells are discussed...
  4. pmc Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1
    Juan Qian
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 7:e1002065. 2011
    ..In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity...
  5. pmc Hope and fear for interferon: the receptor-centric outlook on the future of interferon therapy
    Serge Y Fuchs
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    J Interferon Cytokine Res 33:211-25. 2013
    ..We further hypothesize that activation of these eliminative pathways enables the escape from IFN1-driven suppression of tumorigenesis and elicits the primary refractoriness of tumor to the pharmaceutical IFN1...
  6. pmc Ubiquitination-mediated regulation of interferon responses
    Serge Y Fuchs
    Department of Animal Biology and Mari Lowe Comparative Oncology Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    Growth Factors 30:141-8. 2012
    ..In this mini-review, we highlight recent advances in our understanding of these ubiquitin-mediated mechanisms, their exploitation by invading viruses, and their possible utilization for medical intervention...
  7. ncbi request reprint De-regulation of ubiquitin-dependent proteolysis and the pathogenesis of malignant melanoma
    Serge Y Fuchs
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA
    Cancer Metastasis Rev 24:329-38. 2005
    ..Targeting the ubiquitination and degradation of these pivotal proteins may provide a promising new therapeutic approach to treatment of this disease...
  8. ncbi request reprint Tumor suppressor activities of the Fbw7 E3 ubiquitin ligase receptor
    Serge Y Fuchs
    Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104 6046, USA
    Cancer Biol Ther 4:506-8. 2005
    ..Delineation of the mechanisms of Fbw7 anti-oncogenic activities and of its inactivation in human cancers is expected to gain an important insight into tumorigenesis...
  9. doi request reprint MYC-induced sensitivity of human malignant melanoma to proteasome inhibitors - a KaMYCaze effect
    Serge Y Fuchs
    Pigment Cell Melanoma Res 21:9-10. 2008
  10. pmc Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2
    Hui Zheng
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    Mol Cell Biol 31:710-20. 2011
    ..The mechanisms of the ligand-inducible elimination of IFNAR1 are discussed, along with the potential medical significance of this regulation...
  11. ncbi request reprint Stability of homologue of Slimb F-box protein is regulated by availability of its substrate
    Ying Li
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 279:11074-80. 2004
    ..These findings may define a mechanism for maintaining activities of specific SCF complexes based on availability of a particular substrate...
  12. pmc Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex
    Douglas I Lin
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 24:355-66. 2006
    ..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1...
  13. ncbi request reprint The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer
    Serge Y Fuchs
    Department of Animal Biology, University of Pennsylvania, 3800 Spruce Street, Rm 161E, Philadelphia, PA 19104, USA
    Oncogene 23:2028-36. 2004
    ..Mechanisms underlying beta-TrCP regulation and their aberration in human and animal cancer as well as prospective of targeting beta-TrCP as a means of anticancer therapy are also discussed...
  14. ncbi request reprint Recognition of substrate and Skp1 by the Homologue of Slimb (HOS) ubiquitin ligase receptor D role of the F-box
    Jason R Herter
    Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104 6046, USA
    Med Sci Monit 8:BR283-8. 2002
    ..HOS is a WD40 repeats/F-box-containing protein that actually associates with the substrates and binds to Skp1 via the F-box...
  15. ncbi request reprint Cross-talk between APC/C and CBP/p300
    Jianghuai Liu
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6046, USA
    Cancer Biol Ther 5:760-2. 2006
    ..These findings have profound implications in unveiling additional functions and regulatory mechanisms of these two seemingly independent molecular modulators...
  16. ncbi request reprint The role of ubiquitin-proteasome pathway in oncogenic signaling
    Serge Y Fuchs
    Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104 6046, USA
    Cancer Biol Ther 1:337-41. 2002
    ..This article attempts to briefly overview the role of UPP in the regulation of several signal transduction pathways that contribute to development of cancer...
  17. doi request reprint Oncogene-mediated inhibition of glycogen synthase kinase 3 beta impairs degradation of prolactin receptor
    Alexander Plotnikov
    Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104 4539, USA
    Cancer Res 68:1354-61. 2008
    ....
  18. ncbi request reprint Targeting beta-transducin repeat-containing protein E3 ubiquitin ligase augments the effects of antitumor drugs on breast cancer cells
    Weigang Tang
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6046, USA
    Cancer Res 65:1904-8. 2005
    ..These data provide the proof of principle that targeting beta-TrCP might be beneficial for anticancer therapies...
  19. pmc SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor
    K G Suresh Kumar
    Department of Animal Biology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104 6046, USA
    EMBO J 22:5480-90. 2003
    ..These findings characterize SCF(HOS) as an E3 ubiquitin ligase that is essential for ubiquitination, proteolysis and down-regulation of IFNAR1, and implicate HOS in the regulation of cellular responses to IFNalpha...
  20. ncbi request reprint Phosphorylation and specific ubiquitin acceptor sites are required for ubiquitination and degradation of the IFNAR1 subunit of type I interferon receptor
    K G Suresh Kumar
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 279:46614-20. 2004
    ..We discuss the complexities and specifics of the ubiquitination and degradation of IFNAR1, which is a beta-Trcp substrate that undergoes degradation via a lysosomal pathway...
  21. pmc Negative regulation of prolactin receptor stability and signaling mediated by SCF(beta-TrCP) E3 ubiquitin ligase
    Ying Li
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 24:4038-48. 2004
    ..These data indicate that PRLR is a novel SCF(beta-TrCP) substrate and implicate beta-TrCP as an important negative regulator of PRL signaling and cellular responses to this hormone...
  22. pmc Basal ubiquitin-independent internalization of interferon alpha receptor is prevented by Tyk2-mediated masking of a linear endocytic motif
    K G Suresh Kumar
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:18566-72. 2008
    ..These data delineate a long-sought ligand- and ubiquitin-independent mechanism by which Tyk2 contributes to both the regulation of total IFNAR1 levels as well as the regulation of the cell surface density of this receptor chain...
  23. pmc Polyubiquitination of prolactin receptor stimulates its internalization, postinternalization sorting, and degradation via the lysosomal pathway
    Bentley Varghese
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, 380 S Philadelphia, PA 19104 4539, USA
    Mol Cell Biol 28:5275-87. 2008
    ..We discuss how specific ubiquitination may regulate early and late stages of endocytosis of PRLr and of related receptors to contribute to the negative regulation of the magnitude and duration of downstream signaling...
  24. ncbi request reprint Interaction of Epstein-Barr virus latent membrane protein 1 with SCFHOS/beta-TrCP E3 ubiquitin ligase regulates extent of NF-kappaB activation
    Weigang Tang
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 278:48942-9. 2003
    ..We discuss the potential role of this mechanism in transforming and cytostatic effects of LMP1 variants in cells and Epstein-Barr virus-associated tumors...
  25. pmc Ligand-independent pathway that controls stability of interferon alpha receptor
    Jianghuai Liu
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology Research, School of Veterinary Medicine, University of Pennsylvania, Room 316 Hill Pavilion, 380 S University Avenue, Philadelphia, PA 19104 4539, USA
    Biochem Biophys Res Commun 367:388-93. 2008
    ..We discuss the signaling events that might lead to ubiquitination and degradation of IFNAR1 via ligand-dependent and independent pathways and their potential physiologic significance...
  26. pmc Raf inhibitor stabilizes receptor for the type I interferon but inhibits its anti-proliferative effects in human malignant melanoma cells
    K G Suresh Kumar
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 6:1437-41. 2007
    ..We discuss the implications of this result for combination therapy with BAY 43-9006 and IFNalpha in melanoma patients...
  27. ncbi request reprint Oncogenic beta-catenin signaling networks in colorectal cancer
    Serge Y Fuchs
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Cell Cycle 4:1522-39. 2005
    ....
  28. pmc Inducible priming phosphorylation promotes ligand-independent degradation of the IFNAR1 chain of type I interferon receptor
    Sabyasachi Bhattacharya
    Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:2318-25. 2010
    ..These events play an important role in regulating ubiquitination and degradation of IFNAR1 as well as the extent of Type I interferon signaling...
  29. pmc Impaired turnover of prolactin receptor contributes to transformation of human breast cells
    Alexandr Plotnikov
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 4539, USA
    Cancer Res 69:3165-72. 2009
    ..Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed...
  30. ncbi request reprint Ubiquitin-dependent activation of NF-kappaB: K63-linked ubiquitin chains: a link to cancer?
    Zhijian J Chen
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Cancer Biol Ther 3:286-8. 2004
    ..Recent discoveries of the novel roles of lysine 63-linked polyubiquitin chains in the activation of NF-kappaB transcription factor shed new light on both the mechanistic aspects of this signal transduction pathway and its role in cancer...
  31. ncbi request reprint CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling
    Felicite K Noubissi
    Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    Nature 441:898-901. 2006
    ....
  32. ncbi request reprint Inhibition of HOS expression and activities by Wnt pathway
    Vladimir S Spiegelman
    AMC Cancer Research Center, Lakewood, Colorado, CO 80214, USA
    Oncogene 21:856-60. 2002
    ..These results indicate that expression and activities of HOS are negatively regulated by Wnt/beta-catenin pathway...
  33. ncbi request reprint Elevated expression of Wnt antagonists is a common event in hepatoblastomas
    Arend Koch
    Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
    Clin Cancer Res 11:4295-304. 2005
    ..We propose that Nkd-1 and beta-TrCP may be used as possible diagnostic markers for the activated Wnt signaling pathway in hepatoblastomas...
  34. ncbi request reprint Associations among beta-TrCP, an E3 ubiquitin ligase receptor, beta-catenin, and NF-kappaB in colorectal cancer
    Andrei Ougolkov
    Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, 13 1 Takara machi, Kanazawa 920 0934, Japan
    J Natl Cancer Inst 96:1161-70. 2004
    ..We analyzed expression of beta-TrCP in colorectal cancers and its association with types of beta-catenin subcellular localization, an indirect measure of activation...
  35. ncbi request reprint Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-kappaB
    Neehar Bhatia
    AMC Cancer Research Center, Lakewood, CO 80214, USA
    Oncogene 21:1501-9. 2002
    ..The role of mHOS in the constitutive activation of NF-kappaB in skin carcinogenesis is discussed...
  36. ncbi request reprint Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling
    Vladimir S Spiegelman
    AMC Cancer Research Center, Lakewood, Colorado 80214, USA
    J Biol Chem 277:36624-30. 2002
    ..These data link the induction of HOS in proliferating cells with mitogen-signaling-dependent inhibition of cell differentiation and promotion of cell transformation...
  37. ncbi request reprint Radiation resistance of human melanoma analysed by retroviral insertional mutagenesis reveals a possible role for dopachrome tautomerase
    Brian J Pak
    Molecular and Cellular Biology, Sunnybrook and Women s College Health Sciences Centre and Toronto Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, Ontario, Canada
    Oncogene 23:30-8. 2004
    ....
  38. ncbi request reprint Determinants of growth hormone receptor down-regulation
    Luqin Deng
    Department of Cell Biology, Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294 0012, USA
    Mol Endocrinol 21:1537-51. 2007
    ..The latter requires GH-induced JAK2 activation and GHR tyrosine phosphorylation and is correlated to GHR ubiquitination in our reconstitution system...
  39. pmc UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity
    Oxana A Malakhova
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 25:2358-67. 2006
    ..These data implicate Ubp43 as a novel in vivo inhibitor of signal transduction pathways that are specifically triggered by type I IFN...

Research Grants2

  1. Regulation of interferon receptor by Leishmania kinase
    SERGE FUCHS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  2. Stability of prolactin receptor and prolactin signaling
    Serge Y Fuchs; Fiscal Year: 2010
    ....