Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 286 (5438): 309-312

Copyright © 1999 by the American Association for the Advancement of Science

The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase

Claudio A. P. Joazeiro, 1 Simon S. Wing, 2 Han-kuei Huang, 1 Joel D. Leverson, 1 Tony Hunter, 1* Yun-Cai Liu 3

Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination pathways that recognize target substrates and promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can recognize tyrosine-phosphorylated substrates, such as the activated platelet-derived growth factor receptor, through its SH2 domain and that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING domain. These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system.

1 The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA.
2 Department of Medicine, McGill University, Montreal, Quebec H3A 2B2, Canada.
3 La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
*   To whom correspondence should be addressed. E-mail: hunter{at}salk.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system.
S. J. L. van Wijk, S. J. de Vries, P. Kemmeren, A. Huang, R. Boelens, A. M. J. J. Bonvin, and H. T. M. Timmers (2014)
Mol Syst Biol 5, 295
   Abstract »    Full Text »    PDF »
E3 ubiquitin ligases and human papillomavirus-induced carcinogenesis.
Z. Lou and S. Wang (2014)
Journal of International Medical Research 42, 247-260
   Abstract »    Full Text »    PDF »
CD2-associated Protein (CD2AP) Enhances Casitas B Lineage Lymphoma-3/c (Cbl-3/c)-mediated Ret Isoform-specific Ubiquitination and Degradation via Its Amino-terminal Src Homology 3 Domains.
G. N. Calco, O. R. Stephens, L. M. Donahue, C. C. Tsui, and B. A. Pierchala (2014)
J. Biol. Chem. 289, 7307-7319
   Abstract »    Full Text »    PDF »
Expression of the Immune Regulator Tripartite-Motif 21 Is Controlled by IFN Regulatory Factors.
M. Sjostrand, A. Ambrosi, S. Brauner, J. Sullivan, S. Malin, V. K. Kuchroo, A. Espinosa, and M. Wahren-Herlenius (2013)
J. Immunol. 191, 3753-3763
   Abstract »    Full Text »    PDF »
CBL Linker Region and RING Finger Mutations Lead to Enhanced Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Signaling via Elevated Levels of JAK2 and LYN.
M. Javadi, T. D. Richmond, K. Huang, and D. L. Barber (2013)
J. Biol. Chem. 288, 19459-19470
   Abstract »    Full Text »    PDF »
Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis.
S. T. Lee, M. Feng, Y. Wei, Z. Li, Y. Qiao, P. Guan, X. Jiang, C. H. Wong, K. Huynh, J. Wang, et al. (2013)
PNAS 110, 11121-11126
   Abstract »    Full Text »    PDF »
Tripartite Motif Ligases Catalyze Polyubiquitin Chain Formation through a Cooperative Allosteric Mechanism.
F. C. Streich Jr., V. P. Ronchi, J. P. Connick, and A. L. Haas (2013)
J. Biol. Chem. 288, 8209-8221
   Abstract »    Full Text »    PDF »
Direct and Indirect Control of Mitogen-activated Protein Kinase Pathway-associated Components, BRAP/IMP E3 Ubiquitin Ligase and CRAF/RAF1 Kinase, by the Deubiquitylating Enzyme USP15.
S. D. Hayes, H. Liu, E. MacDonald, C. M. Sanderson, J. M. Coulson, M. J. Clague, and S. Urbe (2012)
J. Biol. Chem. 287, 43007-43018
   Abstract »    Full Text »    PDF »
Flt3 inhibitor AC220 is a potent therapy in a mouse model of myeloproliferative disease driven by enhanced wild-type Flt3 signaling.
S. J. Taylor, S. A. Dagger, C. B. F. Thien, M. E. Wikstrom, and W. Y. Langdon (2012)
Blood 120, 4049-4057
   Abstract »    Full Text »    PDF »
Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy.
S. Cohen, B. Zhai, S. P. Gygi, and A. L. Goldberg (2012)
J. Cell Biol. 198, 575-589
   Abstract »    Full Text »    PDF »
The Ubiquitin E3 Ligase LOSS OF GDU2 Is Required for GLUTAMINE DUMPER1-Induced Amino Acid Secretion in Arabidopsis.
R. Pratelli, D. D. Guerra, S. Yu, M. Wogulis, E. Kraft, W. B. Frommer, J. Callis, and G. Pilot (2012)
Plant Physiology 158, 1628-1642
   Abstract »    Full Text »    PDF »
c-Cbl Ubiquitin Ligase Regulates Focal Adhesion Protein Turnover and Myofibril Degeneration Induced by Neutrophil Protease Cathepsin G.
K. Rafiq, J. Guo, L. Vlasenko, X. Guo, M. A. Kolpakov, A. Sanjay, S. R. Houser, and A. Sabri (2012)
J. Biol. Chem. 287, 5327-5339
   Abstract »    Full Text »    PDF »
The role of ubiquitylation in receptor endocytosis and endosomal sorting.
K. Haglund and I. Dikic (2012)
J. Cell Sci. 125, 265-275
   Abstract »    Full Text »    PDF »
Potentiation of Platelet-Derived Growth Factor Receptor-{beta} Signaling Mediated by Integrin-Associated MFG-E8.
S.-i. Motegi, S. Garfield, X. Feng, M. Sardy, and M. C. Udey (2011)
Arterioscler Thromb Vasc Biol 31, 2653-2664
   Abstract »    Full Text »    PDF »
Ubiquitin-mediated Regulation of CD86 Protein Expression by the Ubiquitin Ligase Membrane-associated RING-CH-1 (MARCH1).
K. Corcoran, M. Jabbour, C. Bhagwandin, M. J. Deymier, D. L. Theisen, and L. Lybarger (2011)
J. Biol. Chem. 286, 37168-37180
   Abstract »    Full Text »    PDF »
CIN85 drives B cell responses by linking BCR signals to the canonical NF-{kappa}B pathway.
K. Kometani, T. Yamada, Y. Sasaki, T. Yokosuka, T. Saito, K. Rajewsky, M. Ishiai, M. Hikida, and T. Kurosaki (2011)
J. Exp. Med. 208, 1447-1457
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor 3 (FGFR3) Is a Strong Heat Shock Protein 90 (Hsp90) Client: IMPLICATIONS FOR THERAPEUTIC MANIPULATION.
M. B. Laederich, C. R. Degnin, G. P. Lunstrum, P. Holden, and W. A. Horton (2011)
J. Biol. Chem. 286, 19597-19604
   Abstract »    Full Text »    PDF »
Hrs Recognizes a Hydrophobic Amino Acid Cluster in Cytokine Receptors during Ubiquitin-independent Endosomal Sorting.
Y. Amano, Y. Yamashita, K. Kojima, K. Yoshino, N. Tanaka, K. Sugamura, and T. Takeshita (2011)
J. Biol. Chem. 286, 15458-15472
   Abstract »    Full Text »    PDF »
A Systematic Search for Endoplasmic Reticulum (ER) Membrane-associated RING Finger Proteins Identifies Nixin/ZNRF4 as a Regulator of Calnexin Stability and ER Homeostasis.
A. Neutzner, M. Neutzner, A.-S. Benischke, S.-W. Ryu, S. Frank, R. J. Youle, and M. Karbowski (2011)
J. Biol. Chem. 286, 8633-8643
   Abstract »    Full Text »    PDF »
Essential Role of E3 Ubiquitin Ligase Activity in Cbl-b-Regulated T Cell Functions.
M. Paolino, C. B. F. Thien, T. Gruber, R. Hinterleitner, G. Baier, W. Y. Langdon, and J. M. Penninger (2011)
J. Immunol. 186, 2138-2147
   Abstract »    Full Text »    PDF »
A CSF-1 Receptor Phosphotyrosine 559 Signaling Pathway Regulates Receptor Ubiquitination and Tyrosine Phosphorylation.
Y. Xiong, D. Song, Y. Cai, W. Yu, Y.-G. Yeung, and E. R. Stanley (2011)
J. Biol. Chem. 286, 952-960
   Abstract »    Full Text »    PDF »
Bifunctional Apoptosis Regulator (BAR), an Endoplasmic Reticulum (ER)-associated E3 Ubiquitin Ligase, Modulates BI-1 Protein Stability and Function in ER Stress.
J. Rong, L. Chen, J. I. Toth, M. Tcherpakov, M. D. Petroski, and J. C. Reed (2011)
J. Biol. Chem. 286, 1453-1463
   Abstract »    Full Text »    PDF »
The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability.
T. M. Durcan, M. Kontogiannea, T. Thorarinsdottir, L. Fallon, A. J. Williams, A. Djarmati, T. Fantaneanu, H. L. Paulson, and E. A. Fon (2011)
Hum. Mol. Genet. 20, 141-154
   Abstract »    Full Text »    PDF »
As4S4 targets RING-type E3 ligase c-CBL to induce degradation of BCR-ABL in chronic myelogenous leukemia.
J.-H. Mao, X.-Y. Sun, J.-X. Liu, Q.-Y. Zhang, P. Liu, Q.-H. Huang, K. K. Li, Q. Chen, Z. Chen, and S.-J. Chen (2010)
PNAS 107, 21683-21688
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor Signaling Crosstalk in Skeletogenesis.
H. Miraoui and P. J. Marie (2010)
Science Signaling 3, re9
   Abstract »    Full Text »    PDF »
Deregulated Intracellular Signaling by Mutated c-CBL in Myeloid Neoplasms.
S. Ogawa, L.-Y. Shih, T. Suzuki, M. Otsu, H. Nakauchi, H. P. Koeffler, and M. Sanada (2010)
Clin. Cancer Res. 16, 3825-3831
   Abstract »    Full Text »    PDF »
The N Terminus of Cbl-c Regulates Ubiquitin Ligase Activity by Modulating Affinity for the Ubiquitin-conjugating Enzyme.
P. E. Ryan, N. Sivadasan-Nair, M. M. Nau, S. Nicholas, and S. Lipkowitz (2010)
J. Biol. Chem. 285, 23687-23698
   Abstract »    Full Text »    PDF »
Ubiquitination-Dependent Regulation of Signaling Receptors in Cancer.
W.-C. HuangFu and S. Y. Fuchs (2010)
Genes & Cancer 1, 725-734
   Abstract »    Full Text »    PDF »
c-Cbl deficiency leads to diminished lymphocyte development and functions in an age-dependent manner.
C. Rathinam and R. A. Flavell (2010)
PNAS 107, 8316-8321
   Abstract »    Full Text »    PDF »
Genomic and phylogenetic characterization of Merino Walk virus, a novel arenavirus isolated in South Africa.
G. Palacios, N. Savji, J. Hui, A. Travassos da Rosa, V. Popov, T. Briese, R. Tesh, and W. I. Lipkin (2010)
J. Gen. Virol. 91, 1315-1324
   Abstract »    Full Text »    PDF »
Increased EFG- and PDGF{alpha}-receptor signaling by mutant FGF-receptor 2 contributes to osteoblast dysfunction in Apert craniosynostosis.
H. Miraoui, J. Ringe, T. Haupl, and P. J. Marie (2010)
Hum. Mol. Genet. 19, 1678-1689
   Abstract »    Full Text »    PDF »
c-Cbl Promotes T Cell Receptor-induced Thymocyte Apoptosis by Activating the Phosphatidylinositol 3-Kinase/Akt Pathway.
C. B. F. Thien, S. A. Dagger, J. H. Steer, F. Koentgen, E. S. Jansen, C. L. Scott, and W. Y. Langdon (2010)
J. Biol. Chem. 285, 10969-10981
   Abstract »    Full Text »    PDF »
Sulindac Metabolites Induce Proteosomal and Lysosomal Degradation of the Epidermal Growth Factor Receptor.
H. A. Pangburn, D. J. Ahnen, and P. L. Rice (2010)
Cancer Prevention Research 3, 560-572
   Abstract »    Full Text »    PDF »
Ubiquitination and degradation of the thrombopoietin receptor c-Mpl.
S. J. Saur, V. Sangkhae, A. E. Geddis, K. Kaushansky, and I. S. Hitchcock (2010)
Blood 115, 1254-1263
   Abstract »    Full Text »    PDF »
SHIP2 (SH2 Domain-containing Inositol Phosphatase 2) SH2 Domain Negatively Controls SHIP2 Monoubiquitination in Response to Epidermal Growth Factor.
J. De Schutter, A. Guillabert, V. Imbault, C. Degraef, C. Erneux, D. Communi, and I. Pirson (2009)
J. Biol. Chem. 284, 36062-36076
   Abstract »    Full Text »    PDF »
Leukocyte Ig-like Receptor B4 (LILRB4) Is a Potent Inhibitor of Fc{gamma}RI-mediated Monocyte Activation via Dephosphorylation of Multiple Kinases.
H. K. Lu, C. Rentero, M. J. Raftery, L. Borges, K. Bryant, and N. Tedla (2009)
J. Biol. Chem. 284, 34839-34848
   Abstract »    Full Text »    PDF »
Cell cycle deregulation by a poxvirus partial mimic of anaphase-promoting complex subunit 11.
M. Mo, S. B. Fleming, and A. A. Mercer (2009)
PNAS 106, 19527-19532
   Abstract »    Full Text »    PDF »
E3 ligase-defective Cbl mutants lead to a generalized mastocytosis and myeloproliferative disease.
S. R. Bandi, C. Brandts, M. Rensinghoff, R. Grundler, L. Tickenbrock, G. Kohler, J. Duyster, W. E. Berdel, C. Muller-Tidow, H. Serve, et al. (2009)
Blood 114, 4197-4208
   Abstract »    Full Text »    PDF »
Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination.
X. Guo, L. Nie, L. Esmailzadeh, J. Zhang, J. R. Bender, and M. M. Sadeghi (2009)
J. Biol. Chem. 284, 29376-29382
   Abstract »    Full Text »    PDF »
Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network.
G. Markson, C. Kiel, R. Hyde, S. Brown, P. Charalabous, A. Bremm, J. Semple, J. Woodsmith, S. Duley, K. Salehi-Ashtiani, et al. (2009)
Genome Res. 19, 1905-1911
   Abstract »    Full Text »    PDF »
c-Cbl Tyrosine Kinase-binding Domain Mutant G306E Abolishes the Interaction of c-Cbl with CD38 and Fails to Promote Retinoic Acid-induced Cell Differentiation and G0 Arrest.
M. Shen and A. Yen (2009)
J. Biol. Chem. 284, 25664-25677
   Abstract »    Full Text »    PDF »
(-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at Ser1046/1047 by p38 MAPK in colon cancer cells.
S. Adachi, M. Shimizu, Y. Shirakami, J. Yamauchi, H. Natsume, R. Matsushima-Nishiwaki, S. To, I.B. Weinstein, H. Moriwaki, and O. Kozawa (2009)
Carcinogenesis 30, 1544-1552
   Abstract »    Full Text »    PDF »
Novel Roles of Hakai in Cell Proliferation and Oncogenesis.
A. Figueroa, H. Kotani, Y. Toda, K. Mazan-Mamczarz, E.-C. Mueller, A. Otto, L. Disch, M. Norman, R. M. Ramdasi, M. Keshtgar, et al. (2009)
Mol. Biol. Cell 20, 3533-3542
   Abstract »    Full Text »    PDF »
Syk Tyrosine 317 Negatively Regulates Osteoclast Function via the Ubiquitin-Protein Isopeptide Ligase Activity of Cbl.
W. Zou, J. L. Reeve, H. Zhao, F. P. Ross, and S. L. Teitelbaum (2009)
J. Biol. Chem. 284, 18833-18839
   Abstract »    Full Text »    PDF »
Knockdown of GnT-Va expression inhibits ligand-induced downregulation of the epidermal growth factor receptor and intracellular signaling by inhibiting receptor endocytosis.
H.-B. Guo, H. Johnson, M. Randolph, I. Lee, and M. Pierce (2009)
Glycobiology 19, 547-559
   Abstract »    Full Text »    PDF »
Intranuclear Degradation of Polyglutamine Aggregates by the Ubiquitin-Proteasome System.
A. Iwata, Y. Nagashima, L. Matsumoto, T. Suzuki, T. Yamanaka, H. Date, K. Deoka, N. Nukina, and S. Tsuji (2009)
J. Biol. Chem. 284, 9796-9803
   Abstract »    Full Text »    PDF »
p85{beta} phosphoinositide 3-kinase regulates CD28 coreceptor function.
I. Alcazar, I. Cortes, A. Zaballos, C. Hernandez, D. A. Fruman, D. F. Barber, and A. C. Carrera (2009)
Blood 113, 3198-3208
   Abstract »    Full Text »    PDF »
CBL Exon 8/9 Mutants Activate the FLT3 Pathway and Cluster in Core Binding Factor/11q Deletion Acute Myeloid Leukemia/Myelodysplastic Syndrome Subtypes.
C. Reindl, H. Quentmeier, K. Petropoulos, P. A. Greif, T. Benthaus, B. Argiropoulos, G. Mellert, S. Vempati, J. Duyster, C. Buske, et al. (2009)
Clin. Cancer Res. 15, 2238-2247
   Abstract »    Full Text »    PDF »
Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis of TRF1.
Y. R. Her and I. K. Chung (2009)
J. Biol. Chem. 284, 8557-8566
   Abstract »    Full Text »    PDF »
Control of Rapsyn Stability by the CUL-3-containing E3 Ligase Complex.
S. Nam, K. Min, H. Hwang, H.-o. Lee, J. H. Lee, J. Yoon, H. Lee, S. Park, and J. Lee (2009)
J. Biol. Chem. 284, 8195-8206
   Abstract »    Full Text »    PDF »
A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration.
J. Chu, N. A. Hong, C. A. Masuda, B. V. Jenkins, K. A. Nelms, C. C. Goodnow, R. J. Glynne, H. Wu, E. Masliah, C. A. P. Joazeiro, et al. (2009)
PNAS 106, 2097-2103
   Abstract »    Full Text »    PDF »
The Ubiquitin Ligase c-Cbl Down-Regulates Fc{gamma}RIIa Activation in Human Neutrophils.
L. Marois, M. Vaillancourt, S. Marois, S. Proulx, G. Pare, E. Rollet-Labelle, and P. H. Naccache (2009)
J. Immunol. 182, 2374-2384
   Abstract »    Full Text »    PDF »
Met Receptor Tyrosine Kinase Degradation Is Altered in Response to the Leucine-rich Repeat of the Listeria Invasion Protein Internalin B.
X. Gao, M. Lorinczi, K. S. Hill, N. C. Brooks, H. Dokainish, K. Ireton, and L. A. Elferink (2009)
J. Biol. Chem. 284, 774-783
   Abstract »    Full Text »    PDF »
250K Single Nucleotide Polymorphism Array Karyotyping Identifies Acquired Uniparental Disomy and Homozygous Mutations, Including Novel Missense Substitutions of c-Cbl, in Myeloid Malignancies.
A. J. Dunbar, L. P. Gondek, C. L. O'Keefe, H. Makishima, M. S. Rataul, H. Szpurka, M. A. Sekeres, X. F. Wang, M. A. McDevitt, and J. P. Maciejewski (2008)
Cancer Res. 68, 10349-10357
   Abstract »    Full Text »    PDF »
c-Cbl Interacts with CD38 and Promotes Retinoic Acid-Induced Differentiation and G0 Arrest of Human Myeloblastic Leukemia Cells.
M. Shen and A. Yen (2008)
Cancer Res. 68, 8761-8769
   Abstract »    Full Text »    PDF »
A Dictyostelium homologue of the metazoan Cbl proteins regulates STAT signalling.
J. Langenick, T. Araki, Y. Yamada, and J. G. Williams (2008)
J. Cell Sci. 121, 3524-3530
   Abstract »    Full Text »    PDF »
Requirement of Rad5 for DNA Polymerase {zeta}-Dependent Translesion Synthesis in Saccharomyces cerevisiae.
V. Pages, A. Bresson, N. Acharya, S. Prakash, R. P. Fuchs, and L. Prakash (2008)
Genetics 180, 73-82
   Abstract »    Full Text »    PDF »
Suppression of c-Cbl Tyrosine Phosphorylation Inhibits Neointimal Formation in Balloon-Injured Rat Arteries.
Z. Tang, Y. Wang, Y. Fan, Y. Zhu, S. Chien, and N. Wang (2008)
Circulation 118, 764-772
   Abstract »    Full Text »    PDF »
Ubc4/5 and c-Cbl Continue to Ubiquitinate EGF Receptor after Internalization to Facilitate Polyubiquitination and Degradation.
K. Umebayashi, H. Stenmark, and T. Yoshimori (2008)
Mol. Biol. Cell 19, 3454-3462
   Abstract »    Full Text »    PDF »
c-Cbl expression levels regulate the functional responses of human central and effector memory CD4 T cells.
N. C. Brembilla, J. Weber, D. Rimoldi, S. Pradervand, F. Schutz, G. Pantaleo, C. Ruegg, M. Quadroni, K. Harshman, and M.-A. Doucey (2008)
Blood 112, 652-660
   Abstract »    Full Text »    PDF »
Cue1p Is an Activator of Ubc7p E2 Activity in Vitro and in Vivo.
O. A. Bazirgan and R. Y. Hampton (2008)
J. Biol. Chem. 283, 12797-12810
   Abstract »    Full Text »    PDF »
A Tale of Two Cbls: Interplay of c-Cbl and Cbl-b in Epidermal Growth Factor Receptor Downregulation.
S. Pennock and Z. Wang (2008)
Mol. Cell. Biol. 28, 3020-3037
   Abstract »    Full Text »    PDF »
Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis.
B. Gao, S.-M. Lee, A. Chen, J. Zhang, D. D. Zhang, K. Kannan, R. A. Ortmann, and D. Fang (2008)
EMBO Rep. 9, 480-485
   Abstract »    Full Text »    PDF »
The E3 ubiquitin ligase c-Cbl restricts development and functions of hematopoietic stem cells.
C. Rathinam, C. B.F. Thien, W. Y. Langdon, H. Gu, and R. A. Flavell (2008)
Genes & Dev. 22, 992-997
   Abstract »    Full Text »    PDF »
T-Cell Receptor-Induced NF-{kappa}B Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b.
G. Qiao, Z. Li, L. Molinero, M.-L. Alegre, H. Ying, Z. Sun, J. M. Penninger, and J. Zhang (2008)
Mol. Cell. Biol. 28, 2470-2480
   Abstract »    Full Text »    PDF »
Novel Pro-survival Functions of the Kruppel-like Transcription Factor Egr2 in Promotion of Macrophage Colony-stimulating Factor-mediated Osteoclast Survival Downstream of the MEK/ERK Pathway.
E. W. Bradley, M. M. Ruan, and M. J. Oursler (2008)
J. Biol. Chem. 283, 8055-8064
   Abstract »    Full Text »    PDF »
Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.
C. Ng, R. A. Jackson, J. P. Buschdorf, Q. Sun, G. R. Guy, and J. Sivaraman (2008)
EMBO J. 27, 804-816
   Abstract »    Full Text »    PDF »
Transforming growth factor-{beta} signaling and ubiquitinators in cancer.
E. Glasgow and L. Mishra (2008)
Endocr. Relat. Cancer 15, 59-72
   Abstract »    Full Text »    PDF »
Stem cell factor affects fate determination of human gonocytes in vitro.
J. Tu, L. Fan, K. Tao, W. Zhu, J. Li, and G. Lu (2007)
Reproduction 134, 757-765
   Abstract »    Full Text »    PDF »
Amplitude Control of Protein Kinase C by RINCK, a Novel E3 Ubiquitin Ligase.
D. Chen, C. Gould, R. Garza, T. Gao, R. Y. Hampton, and A. C. Newton (2007)
J. Biol. Chem. 282, 33776-33787
   Abstract »    Full Text »    PDF »
A Novel Interaction between Atrophin-interacting Protein 4 and beta-p21-activated Kinase-interactive Exchange Factor Is Mediated by an SH3 Domain.
J. M. Janz, T. P. Sakmar, and K. C. Min (2007)
J. Biol. Chem. 282, 28893-28903
   Abstract »    Full Text »    PDF »
Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins.
H. Sun, J. D. Leverson, and T. Hunter (2007)
EMBO J. 26, 4102-4112
   Abstract »    Full Text »    PDF »
Degradation of HER2 by Cbl-Based Chimeric Ubiquitin Ligases.
X. Li, L. Shen, J. Zhang, J. Su, L. Shen, X. Liu, H. Han, W. Han, and L. Yao (2007)
Cancer Res. 67, 8716-8724
   Abstract »    Full Text »    PDF »
Arenavirus Z-Glycoprotein Association Requires Z Myristoylation but Not Functional RING or Late Domains.
A. A. Capul, M. Perez, E. Burke, S. Kunz, M. J. Buchmeier, and J. C. de la Torre (2007)
J. Virol. 81, 9451-9460
   Abstract »    Full Text »    PDF »
Flt3-dependent transformation by inactivating c-Cbl mutations in AML.
B. Sargin, C. Choudhary, N. Crosetto, M. H. H. Schmidt, R. Grundler, M. Rensinghoff, C. Thiessen, L. Tickenbrock, J. Schwable, C. Brandts, et al. (2007)
Blood 110, 1004-1012
   Abstract »    Full Text »    PDF »
GAPex-5 Mediates Ubiquitination, Trafficking, and Degradation of Epidermal Growth Factor Receptor.
X. Su, C. Kong, and P. D. Stahl (2007)
J. Biol. Chem. 282, 21278-21284
   Abstract »    Full Text »    PDF »
The Src-like Adaptor Protein 2 Regulates Colony-stimulating Factor-1 Receptor Signaling and Down-regulation.
B. Pakuts, C. Debonneville, L. M. Liontos, M. P. Loreto, and C. J. McGlade (2007)
J. Biol. Chem. 282, 17953-17963
   Abstract »    Full Text »    PDF »
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function.
J. J. Yi and M. D. Ehlers (2007)
Pharmacol. Rev. 59, 14-39
   Abstract »    Full Text »    PDF »
Characterization of Multiple Multivesicular Body Sorting Determinants within Sna3: A Role for the Ubiquitin Ligase Rsp5.
A. J. Oestreich, M. Aboian, J. Lee, I. Azmi, J. Payne, R. Issaka, B. A. Davies, and D. J. Katzmann (2007)
Mol. Biol. Cell 18, 707-720
   Abstract »    Full Text »    PDF »
Determinants of RING-E2 Fidelity for Hrd1p, a Membrane-anchored Ubiquitin Ligase.
O. A. Bazirgan, R. M. Garza, and R. Y. Hampton (2006)
J. Biol. Chem. 281, 38989-39001
   Abstract »    Full Text »    PDF »
PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes.
J.-A. Ko, Y. Kimura, K. Matsuura, H. Yamamoto, T. Gondo, and M. Inui (2006)
J. Cell Sci. 119, 5106-5113
   Abstract »    Full Text »    PDF »
Genetic Ablation of the c-Cbl Ubiquitin Ligase Domain Results in Increased Energy Expenditure and Improved Insulin Action.
J. C. Molero, N. Turner, C. B.F. Thien, W. Y. Langdon, D. E. James, and G. J. Cooney (2006)
Diabetes 55, 3411-3417
   Abstract »    Full Text »    PDF »
Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen.
I. Unk, I. Hajdu, K. Fatyol, B. Szakal, A. Blastyak, V. Bermudez, J. Hurwitz, L. Prakash, S. Prakash, and L. Haracska (2006)
PNAS 103, 18107-18112
   Abstract »    Full Text »    PDF »
Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.
L. L. Dragone, M. D. Myers, C. White, S. Gadwal, T. Sosinowski, H. Gu, and A. Weiss (2006)
PNAS 103, 18202-18207
   Abstract »    Full Text »    PDF »
Cbl-b Is a Negative Regulator of Inflammatory Cytokines Produced by IgE-Activated Mast Cells.
S. E. Gustin, C. B. F. Thien, and W. Y. Langdon (2006)
J. Immunol. 177, 5980-5989
   Abstract »    Full Text »    PDF »
Mms2-Ubc13-Dependent and -Independent Roles of Rad5 Ubiquitin Ligase in Postreplication Repair and Translesion DNA Synthesis in Saccharomyces cerevisiae.
V. Gangavarapu, L. Haracska, I. Unk, R. E. Johnson, S. Prakash, and L. Prakash (2006)
Mol. Cell. Biol. 26, 7783-7790
   Abstract »    Full Text »    PDF »
Genetic and Expression Aberrations of E3 Ubiquitin Ligases in Human Breast Cancer.
C. Chen, A. K. Seth, and A. E. Aplin (2006)
Mol. Cancer Res. 4, 695-707
   Abstract »    Full Text »    PDF »
Conjugation to Nedd8 Instigates Ubiquitylation and Down-regulation of Activated Receptor Tyrosine Kinases.
S. Oved, Y. Mosesson, Y. Zwang, E. Santonico, K. Shtiegman, M. D. Marmor, B. S. Kochupurakkal, M. Katz, S. Lavi, G. Cesareni, et al. (2006)
J. Biol. Chem. 281, 21640-21651
   Abstract »    Full Text »    PDF »
NARF, an Nemo-like Kinase (NLK)-associated Ring Finger Protein Regulates the Ubiquitylation and Degradation of T Cell Factor/Lymphoid Enhancer Factor (TCF/LEF).
M. Yamada, J. Ohnishi, B. Ohkawara, S. Iemura, K. Satoh, J. Hyodo-Miura, K. Kawachi, T. Natsume, and H. Shibuya (2006)
J. Biol. Chem. 281, 20749-20760
   Abstract »    Full Text »    PDF »
The Sjogren's Syndrome-Associated Autoantigen Ro52 Is an E3 Ligase That Regulates Proliferation and Cell Death.
A. Espinosa, W. Zhou, M. Ek, M. Hedlund, S. Brauner, K. Popovic, L. Horvath, T. Wallerskog, M. Oukka, F. Nyberg, et al. (2006)
J. Immunol. 176, 6277-6285
   Abstract »    Full Text »    PDF »
Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets..
M. D. Lopez-Avalos, V. F. Duvivier-Kali, G. Xu, S. Bonner-Weir, A. Sharma, and G. C. Weir (2006)
Diabetes 55, 1223-1231
   Abstract »    Full Text »    PDF »
The WD40 Repeats of FANCL Are Required for Fanconi Anemia Core Complex Assembly.
A. M. Gurtan, P. Stuckert, and A. D. D'Andrea (2006)
J. Biol. Chem. 281, 10896-10905
   Abstract »    Full Text »    PDF »
White Spot Syndrome Virus Open Reading Frame 222 Encodes a Viral E3 Ligase and Mediates Degradation of a Host Tumor Suppressor via Ubiquitination.
F. He, B. J. Fenner, A. K. Godwin, and J. Kwang (2006)
J. Virol. 80, 3884-3892
   Abstract »    Full Text »    PDF »
Trim-Cyclophilin A Fusion Proteins Can Restrict Human Immunodeficiency Virus Type 1 Infection at Two Distinct Phases in the Viral Life Cycle.
M. W. Yap, M. P. Dodding, and J. P. Stoye (2006)
J. Virol. 80, 4061-4067
   Abstract »    Full Text »    PDF »
Growth and Motility Inhibition of Breast Cancer Cells by Epidermal Growth Factor Receptor Degradation Is Correlated with Inactivation of Cdc42.
D. S. Hirsch, Y. Shen, and W. J. Wu (2006)
Cancer Res. 66, 3523-3530
   Abstract »    Full Text »    PDF »
Role of Ubiquitylation in Cellular Membrane Transport.
O. Staub and D. Rotin (2006)
Physiol Rev 86, 669-707
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882