Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

Ubiquitination is a reversible posttranslational modification of cellular proteins, in which a 76–amino acid polypeptide, ubiquitin, is primarily attached to the ϵ-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.

[1]  Zhijian J. Chen,et al.  The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. , 2004, Molecular cell.

[2]  M. Komada,et al.  Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes. , 2005, Molecular biology of the cell.

[3]  J. Wrana,et al.  Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. , 2000, Molecular cell.

[4]  Scott D Emr,et al.  The ESCRT complexes: structure and mechanism of a membrane-trafficking network. , 2006, Annual review of biophysics and biomolecular structure.

[5]  K. Helin,et al.  The Ubiquitin Ligase HectH9 Regulates Transcriptional Activation by Myc and Is Essential for Tumor Cell Proliferation , 2005, Cell.

[6]  A. Israël,et al.  Monoubiquitination and endocytosis direct γ-secretase cleavage of activated Notch receptor , 2004, The Journal of cell biology.

[7]  A. Lehmann,et al.  Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. , 2004, Molecular cell.

[8]  M. Komada,et al.  The Hrs/STAM complex in the downregulation of receptor tyrosine kinases. , 2005, Journal of biochemistry.

[9]  Philipp Stelter,et al.  Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation , 2003, Nature.

[10]  Pier Paolo Di Fiore,et al.  Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation , 2003, Nature Cell Biology.

[11]  R. Haguenauer‐Tsapis,et al.  Ubiquitin Lys63 is involved in ubiquitination of a yeast plasma membrane protein , 1997, The EMBO journal.

[12]  A. Brice,et al.  A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K–Akt signalling , 2006, Nature Cell Biology.

[13]  Honglin Zhou,et al.  Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κB activation , 2005, The Journal of experimental medicine.

[14]  Linda Hicke,et al.  Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. , 2003, Annual review of cell and developmental biology.

[15]  C. Pickart,et al.  Ubiquitin: structures, functions, mechanisms. , 2004, Biochimica et biophysica acta.

[16]  J. Yates,et al.  Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain , 2004, Nature Cell Biology.

[17]  L. Hicke.  A New Ticket for Entry into Budding Vesicles—Ubiquitin , 2001, Cell.

[18]  R. Kölling,et al.  The ABC‐transporter Ste6 accumulates in the plasma membrane in a ubiquitinated form in endocytosis mutants. , 1994, The EMBO journal.

[19]  Pier Paolo Di Fiore,et al.  A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins , 2002, Nature.

[20]  L. Schild,et al.  Trafficking and cell surface stability of ENaC. , 2001, American journal of physiology. Renal physiology.

[21]  B. André,et al.  NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains. , 1999, Journal of cell science.

[22]  P. Lehner,et al.  Lysine‐63‐linked ubiquitination is required for endolysosomal degradation of class I molecules , 2006, The EMBO journal.

[23]  John R Yates,et al.  Deubiquitination of Histone H2B by a Yeast Acetyltransferase Complex Regulates Transcription* , 2004, Journal of Biological Chemistry.

[24]  P. Transidico,et al.  Clathrin-independent endocytosis of ubiquitinated cargos. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Honglin Zhou,et al.  Bcl10 activates the NF-κB pathway through ubiquitination of NEMO , 2004, Nature.

[26]  S. Srinivasula,et al.  Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-κB activation , 2006, Nature Cell Biology.

[27]  S. Elsasser,et al.  Delivery of ubiquitinated substrates to protein-unfolding machines , 2005, Nature Cell Biology.

[28]  Howard Riezman,et al.  Ubiquitination of a Yeast Plasma Membrane Receptor Signals Its Ligand-Stimulated Endocytosis , 1996, Cell.

[29]  Zhijian J. Chen,et al.  TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. , 2004, Molecular cell.

[30]  P. De Camilli,et al.  The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  K. Cadwell,et al.  Ubiquitination on Nonlysine Residues by a Viral E3 Ubiquitin Ligase , 2005, Science.

[32]  C. Ross,et al.  Parkin Mediates Nonclassical, Proteasomal-Independent Ubiquitination of Synphilin-1: Implications for Lewy Body Formation , 2005, The Journal of Neuroscience.

[33]  Rein Aasland,et al.  FYVE fingers bind PtdIns(3)P , 1998, Nature.

[34]  Yosef Yarden,et al.  Endocytosis of Receptor Tyrosine Kinases Is Driven by Monoubiquitylation, Not Polyubiquitylation* , 2003, Journal of Biological Chemistry.

[35]  E. Friedberg,et al.  Trading places: how do DNA polymerases switch during translesion DNA synthesis? , 2005, Molecular cell.

[36]  R. Haguenauer‐Tsapis,et al.  Deubiquitination Step in the Endocytic Pathway of Yeast Plasma Membrane Proteins: Crucial Role of Doa4p Ubiquitin Isopeptidase , 2001, Molecular and Cellular Biology.

[37]  Bevil R. Conway,et al.  Cell Surface Trk Receptors Mediate NGF-Induced Survival While Internalized Receptors Regulate NGF-Induced Differentiation , 2000, The Journal of Neuroscience.

[38]  F. Lee,et al.  Cell Survival through Trk Neurotrophin Receptors Is Differentially Regulated by Ubiquitination , 2006, Neuron.

[39]  Jeffrey L. Wrana,et al.  Distinct endocytic pathways regulate TGF-β receptor signalling and turnover , 2003, Nature Cell Biology.

[40]  L. Hicke,et al.  A function for monoubiquitination in the internalization of a G protein-coupled receptor. , 1998, Molecular cell.

[41]  G. Wider,et al.  Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis , 2005, Science.

[42]  T. Kohout,et al.  Regulation of Receptor Fate by Ubiquitination of Activated β2-Adrenergic Receptor and β-Arrestin , 2001, Science.

[43]  M. J. Clague,et al.  Hrs function: viruses provide the clue. , 2003, Trends in cell biology.

[44]  Somasekar Seshagiri,et al.  De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling , 2004, Nature.

[45]  J. McCullough,et al.  AMSH is an endosome-associated ubiquitin isopeptidase , 2004, The Journal of cell biology.

[46]  A. Ciechanover,et al.  The ubiquitin system for protein degradation. , 1992, Annual review of biochemistry.

[47]  Aydin Haririnia,et al.  Solution Conformation of Lys63-linked Di-ubiquitin Chain Provides Clues to Functional Diversity of Polyubiquitin Signaling* , 2004, Journal of Biological Chemistry.

[48]  S. Akira,et al.  TAK1‐binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL‐1 signaling pathway , 2005, Genes to cells : devoted to molecular & cellular mechanisms.

[49]  G. Rubin,et al.  The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta , 2005, Development.

[50]  P. Kaiser,et al.  A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by the 26S proteasome , 2006, Nature Cell Biology.

[51]  Jianxiong Jiang,et al.  Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. , 2005, Molecular cell.

[52]  P. van Kerkhof,et al.  Ubiquitin system-dependent regulation of growth hormone receptor signal transduction. , 2004, Current topics in microbiology and immunology.

[53]  Sebastian A. Wagner,et al.  Regulation of ubiquitin-binding proteins by monoubiquitination , 2006, Nature Cell Biology.

[54]  Xuejun Jiang,et al.  Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. , 2006, Molecular cell.

[55]  T. Kigawa,et al.  Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. , 2001, Science.

[56]  S. Leppla,et al.  Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis , 2006, The Journal of cell biology.

[57]  Linda Hicke,et al.  Ubiquitin-binding domains , 2005, Nature Reviews Molecular Cell Biology.

[58]  Wei Gu,et al.  p53 ubiquitination: Mdm2 and beyond. , 2006, Molecular cell.

[59]  D. Fushman,et al.  Polyubiquitin chains: polymeric protein signals. , 2004, Current opinion in chemical biology.