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.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 12 January 2007:
Vol. 315. no. 5809, pp. 201 - 205
DOI: 10.1126/science.1127085

Review

Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

Debdyuti Mukhopadhyay and Howard Riezman*

Ubiquitination is a reversible posttranslational modification of cellular proteins, in which a 76–amino acid polypeptide, ubiquitin, is primarily attached to the {epsilon}-amino group of lysines in target proteins. Ubiquitination is a major player in regulating a broad host of cellular processes, including cell division, differentiation, signal transduction, protein trafficking, and quality control. Aberrations in the ubiquitination system are implicated in pathogenesis of some diseases, certain malignancies, neurodegenerative disorders, and pathologies of the inflammatory immune response. Here, we discuss the proteasome-independent roles of ubiquitination in signaling and endocytosis.

Department of Biochemistry, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland.

* To whom correspondence should be addressed. E-mail: Howard.Riezman{at}biochem.unige.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Deubiquitinating Enzyme USP10 Regulates the Post-endocytic Sorting of Cystic Fibrosis Transmembrane Conductance Regulator in Airway Epithelial Cells.
J. M. Bomberger, R. L. Barnaby, and B. A. Stanton (2009)
J. Biol. Chem. 284, 18778-18789
   Abstract »    Full Text »    PDF »
TRIM32 is an E3 ubiquitin ligase for dysbindin.
M. Locke, C. L. Tinsley, M. A. Benson, and D. J. Blake (2009)
Hum. Mol. Genet. 18, 2344-2358
   Abstract »    Full Text »    PDF »
The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance.
R. Meller (2009)
Neuroscientist 15, 243-260
   Abstract »    PDF »
K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway.
E. Lauwers, C. Jacob, and B. Andre (2009)
J. Cell Biol. 185, 493-502
   Abstract »    Full Text »    PDF »
Phagocytosis in Macrophages Lacking Cbl Reveals an Unsuspected Role for Fc{gamma} Receptor Signaling and Actin Assembly in Target Binding.
B. M. Dale, D. Traum, H. Erdjument-Bromage, P. Tempst, and S. Greenberg (2009)
J. Immunol. 182, 5654-5662
   Abstract »    Full Text »    PDF »
Properties of the Ubiquitin-Pex5p Thiol Ester Conjugate.
C. P. Grou, A. F. Carvalho, M. P. Pinto, S. J. Huybrechts, C. Sa-Miranda, M. Fransen, and J. E. Azevedo (2009)
J. Biol. Chem. 284, 10504-10513
   Abstract »    Full Text »    PDF »
HSV ICP0 recruits USP7 to modulate TLR-mediated innate response.
S. Daubeuf, D. Singh, Y. Tan, H. Liu, H. J. Federoff, W. J. Bowers, and K. Tolba (2009)
Blood 113, 3264-3275
   Abstract »    Full Text »    PDF »
The E3 ubiquitin ligase LNX1p80 promotes the removal of claudins from tight junctions in MDCK cells.
S. Takahashi, N. Iwamoto, H. Sasaki, M. Ohashi, Y. Oda, S. Tsukita, and M. Furuse (2009)
J. Cell Sci. 122, 985-994
   Abstract »    Full Text »    PDF »
A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases.
C. M. Quezada, S. W. Hicks, J. E. Galan, and C. E. Stebbins (2009)
PNAS 106, 4864-4869
   Abstract »    Full Text »    PDF »
Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.
W. Li, D. Tu, L. Li, T. Wollert, R. Ghirlando, A. T. Brunger, and Y. Ye (2009)
PNAS 106, 3722-3727
   Abstract »    Full Text »    PDF »
SUMO-Specific Protease 1 (SENP1) Reverses the Hormone-Augmented SUMOylation of Androgen Receptor and Modulates Gene Responses in Prostate Cancer Cells.
S. Kaikkonen, T. Jaaskelainen, U. Karvonen, M. M. Rytinki, H. Makkonen, D. Gioeli, B. M. Paschal, and J. J. Palvimo (2009)
Mol. Endocrinol. 23, 292-307
   Abstract »    Full Text »    PDF »
Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response.
J. Wu, M. S. Y. Huen, L.-Y. Lu, L. Ye, Y. Dou, M. Ljungman, J. Chen, and X. Yu (2009)
Mol. Cell. Biol. 29, 849-860
   Abstract »    Full Text »    PDF »
Drought Stress-Induced Rma1H1, a RING Membrane-Anchor E3 Ubiquitin Ligase Homolog, Regulates Aquaporin Levels via Ubiquitination in Transgenic Arabidopsis Plants.
H. K. Lee, S. K. Cho, O. Son, Z. Xu, I. Hwang, and W. T. Kim (2009)
PLANT CELL 21, 622-641
   Abstract »    Full Text »    PDF »
Analysis of nondegradative protein ubiquitylation with a monoclonal antibody specific for lysine-63-linked polyubiquitin.
H. Wang, A. Matsuzawa, S. A. Brown, J. Zhou, C. S. Guy, P.-H. Tseng, K. Forbes, T. P. Nicholson, P. W. Sheppard, H. Hacker, et al. (2008)
PNAS 105, 20197-20202
   Abstract »    Full Text »    PDF »
Discovery of Cellular Regulation by Protein Degradation.
A. Varshavsky (2008)
J. Biol. Chem. 283, 34469-34489
   Full Text »    PDF »
SCCRO (DCUN1D1) Is an Essential Component of the E3 Complex for Neddylation.
A. Y. Kim, C. C. Bommelje, B. E. Lee, Y. Yonekawa, L. Choi, L. G. Morris, G. Huang, A. Kaufman, R. J. H. Ryan, B. Hao, et al. (2008)
J. Biol. Chem. 283, 33211-33220
   Abstract »    Full Text »    PDF »
Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.
N. J. Foot, H. E. Dalton, L. M. Shearwin-Whyatt, L. Dorstyn, S.-S. Tan, B. Yang, and S. Kumar (2008)
Blood 112, 4268-4275
   Abstract »    Full Text »    PDF »
The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis.
P. J. Baugher and A. Richmond (2008)
J. Biol. Chem. 283, 30868-30878
   Abstract »    Full Text »    PDF »
Regulatory Monoubiquitination of Phosphoenolpyruvate Carboxylase in Germinating Castor Oil Seeds.
R. G. Uhrig, Y.-M. She, C. A. Leach, and W. C. Plaxton (2008)
J. Biol. Chem. 283, 29650-29657
   Abstract »    Full Text »    PDF »
TRAF6 and the Three C-Terminal Lysine Sites on IRF7 Are Required for Its Ubiquitination-Mediated Activation by the Tumor Necrosis Factor Receptor Family Member Latent Membrane Protein 1.
S. Ning, A. D. Campos, B. G. Darnay, G. L. Bentz, and J. S. Pagano (2008)
Mol. Cell. Biol. 28, 6536-6546
   Abstract »    Full Text »    PDF »
The Ubiquitin-Protein Ligase Nedd4-2 Differentially Interacts with and Regulates Members of the Tweety Family of Chloride Ion Channels.
Y. He, D. H. Hryciw, M. L. Carroll, S. A. Myers, A. K. Whitbread, S. Kumar, P. Poronnik, and J. D. Hooper (2008)
J. Biol. Chem. 283, 24000-24010
   Abstract »    Full Text »    PDF »
Nedd4 Mediates Agonist-dependent Ubiquitination, Lysosomal Targeting, and Degradation of the {beta}2-Adrenergic Receptor.
S. K. Shenoy, K. Xiao, V. Venkataramanan, P. M. Snyder, N. J. Freedman, and A. M. Weissman (2008)
J. Biol. Chem. 283, 22166-22176
   Abstract »    Full Text »    PDF »
Ubiquitination of Fibroblast Growth Factor Receptor 1 Is Required for Its Intracellular Sorting but Not for Its Endocytosis.
E. M. Haugsten, J. Malecki, S. M. S. Bjorklund, S. Olsnes, and J. Wesche (2008)
Mol. Biol. Cell 19, 3390-3403
   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 »
Brain-derived Neurotrophic Factor-Tropomyosin-related Kinase B Signaling Contributes to Activity-dependent Changes in Synaptic Proteins.
J.-M. Jia, Q. Chen, Y. Zhou, S. Miao, J. Zheng, C. Zhang, and Z.-Q. Xiong (2008)
J. Biol. Chem. 283, 21242-21250
   Abstract »    Full Text »    PDF »
TAB4 Stimulates TAK1-TAB1 Phosphorylation and Binds Polyubiquitin to Direct Signaling to NF-{kappa}B.
T. D. Prickett, J. Ninomiya-Tsuji, P. Broglie, T. L. Muratore-Schroeder, J. Shabanowitz, D. F. Hunt, and D. L. Brautigan (2008)
J. Biol. Chem. 283, 19245-19254
   Abstract »    Full Text »    PDF »
Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene.
F. Capon, M.-J. Bijlmakers, N. Wolf, M. Quaranta, U. Huffmeier, M. Allen, K. Timms, V. Abkevich, A. Gutin, R. Smith, et al. (2008)
Hum. Mol. Genet. 17, 1938-1945
   Abstract »    Full Text »    PDF »
Arabidopsis PUB22 and PUB23 Are Homologous U-Box E3 Ubiquitin Ligases That Play Combinatory Roles in Response to Drought Stress.
S. K. Cho, M. Y. Ryu, C. Song, J. M. Kwak, and W. T. Kim (2008)
PLANT CELL 20, 1899-1914
   Abstract »    Full Text »    PDF »
JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis.
R. Farras, V. Baldin, S. Gallach, C. Acquaviva, G. Bossis, I. Jariel-Encontre, and M. Piechaczyk (2008)
Mol. Cell. Biol. 28, 4173-4187
   Abstract »    Full Text »    PDF »
SPIN1, a K Homology Domain Protein Negatively Regulated and Ubiquitinated by the E3 Ubiquitin Ligase SPL11, Is Involved in Flowering Time Control in Rice.
M. E. Vega-Sanchez, L. Zeng, S. Chen, H. Leung, and G.-L. Wang (2008)
PLANT CELL 20, 1456-1469
   Abstract »    Full Text »    PDF »
Ubiquitin-Proteasome-dependent Degradation of a Mitofusin, a Critical Regulator of Mitochondrial Fusion.
M. M.J. Cohen, G. P. Leboucher, N. Livnat-Levanon, M. H. Glickman, and A. M. Weissman (2008)
Mol. Biol. Cell 19, 2457-2464
   Abstract »    Full Text »    PDF »
A Role for the Cleaved Cytoplasmic Domain of E-cadherin in the Nucleus.
E. C. Ferber, M. Kajita, A. Wadlow, L. Tobiansky, C. Niessen, H. Ariga, J. Daniel, and Y. Fujita (2008)
J. Biol. Chem. 283, 12691-12700
   Abstract »    Full Text »    PDF »
SUMOylation Modulates the Transcription Repressor Function of RIP140.
M. M. Rytinki and J. J. Palvimo (2008)
J. Biol. Chem. 283, 11586-11595
   Abstract »    Full Text »    PDF »
Salmonella Secreted Factor L Deubiquitinase of Salmonella typhimurium Inhibits NF-{kappa}B, Suppresses I{kappa}B{alpha} Ubiquitination and Modulates Innate Immune Responses.
G. Le Negrate, B. Faustin, K. Welsh, M. Loeffler, M. Krajewska, P. Hasegawa, S. Mukherjee, K. Orth, S. Krajewski, A. Godzik, et al. (2008)
J. Immunol. 180, 5045-5056
   Abstract »    Full Text »    PDF »
Essential Role of Sequestosome 1/p62 in Regulating Accumulation of Lys63-ubiquitinated Proteins.
M. W. Wooten, T. Geetha, J. R. Babu, M. L. Seibenhener, J. Peng, N. Cox, M.-T. Diaz-Meco, and J. Moscat (2008)
J. Biol. Chem. 283, 6783-6789
   Abstract »    Full Text »    PDF »
The tumour-associated antigen L6 (L6-Ag) is recruited to the tetraspanin-enriched microdomains: implication for tumour cell motility.
T. Lekishvili, E. Fromm, M. Mujoomdar, and F. Berditchevski (2008)
J. Cell Sci. 121, 685-694
   Abstract »    Full Text »    PDF »
Analysis of Single Nucleotide Polymorphisms Identifies Major Type 1A Diabetes Locus Telomeric of the Major Histocompatibility Complex.
T. A. Aly, E. E. Baschal, M. M. Jahromi, M. S. Fernando, S. R. Babu, T. E. Fingerlin, A. Kretowski, H. A. Erlich, P. R. Fain, M. J. Rewers, et al. (2008)
Diabetes 57, 770-776
   Abstract »    Full Text »    PDF »
Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases.
J. M.M. Tan, E. S.P. Wong, D. S. Kirkpatrick, O. Pletnikova, H. S. Ko, S.-P. Tay, M. W.L. Ho, J. Troncoso, S. P. Gygi, M. K. Lee, et al. (2008)
Hum. Mol. Genet. 17, 431-439
   Abstract »    Full Text »    PDF »
Identification of Human Cytomegalovirus UL84 Virus- and Cell-Encoded Binding Partners by Using Proteomics Analysis.
Y. Gao, K. Colletti, and G. S. Pari (2008)
J. Virol. 82, 96-104
   Abstract »    Full Text »    PDF »
The E1 ubiquitin-activating enzyme Uba1 in Drosophila controls apoptosis autonomously and tissue growth non-autonomously.
T. V. Lee, T. Ding, Z. Chen, V. Rajendran, H. Scherr, M. Lackey, C. Bolduc, and A. Bergmann (2008)
Development 135, 43-52
   Abstract »    Full Text »    PDF »
Expression and Localization of RGS9-2/G 5/R7BP Complex In Vivo Is Set by Dynamic Control of Its Constitutive Degradation by Cellular Cysteine Proteases.
G. R. Anderson, R. Lujan, A. Semenov, M. Pravetoni, E. N. Posokhova, J. H. Song, V. Uversky, C.-K. Chen, K. Wickman, and K. A. Martemyanov (2007)
J. Neurosci. 27, 14117-14127
   Abstract »    Full Text »    PDF »
Histone Deacetylase 6 Regulates Growth Factor-Induced Actin Remodeling and Endocytosis.
Y.-s. Gao, C. C. Hubbert, J. Lu, Y.-S. Lee, J.-Y. Lee, and T.-P. Yao (2007)
Mol. Cell. Biol. 27, 8637-8647
   Abstract »    Full Text »    PDF »
Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex.
H. V. Heemers and D. J. Tindall (2007)
Endocr. Rev. 28, 778-808
   Abstract »    Full Text »    PDF »
The Roles of Kinases in Familial Parkinson's Disease.
M. R. Cookson, W. Dauer, T. Dawson, E. A. Fon, M. Guo, and J. Shen (2007)
J. Neurosci. 27, 11865-11868
   Abstract »    Full Text »    PDF »
Ubiquitination of beta-Arrestin Links Seven-transmembrane Receptor Endocytosis and ERK Activation.
S. K. Shenoy, L. S. Barak, K. Xiao, S. Ahn, M. Berthouze, A. K. Shukla, L. M. Luttrell, and R. J. Lefkowitz (2007)
J. Biol. Chem. 282, 29549-29562
   Abstract »    Full Text »    PDF »
A Conserved Cysteine Is Essential for Pex4p-dependent Ubiquitination of the Peroxisomal Import Receptor Pex5p.
C. Williams, M. van den Berg, R. R. Sprenger, and B. Distel (2007)
J. Biol. Chem. 282, 22534-22543
   Abstract »    Full Text »    PDF »
Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels.
M. Joch, A. R. Ase, C. X.-Q. Chen, P. A. MacDonald, M. Kontogiannea, A. T. Corera, A. Brice, P. Seguela, and E. A. Fon (2007)
Mol. Biol. Cell 18, 3105-3118
   Abstract »    Full Text »    PDF »
Regulation of Receptors and Transporters by Ubiquitination: New Insights into Surprisingly Similar Mechanisms.
M. Miranda and A. Sorkin (2007)
Mol. Interv. 7, 157-167
   Abstract »    Full Text »    PDF »
Seven-Transmembrane Receptors and Ubiquitination.
S. K. Shenoy (2007)
Circ. Res. 100, 1142-1154
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)