Research Topics
Genomes and Genes | M HochstrasserSummaryAffiliation: Yale University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligaseMin Deng
Yale University, Department of Molecular Biophysics and Biochemistry, 266 Whitney Avenue, P O Box 208114, New Haven, Connecticut 06520 8114, USA
Nature 443:827-31. 2006..These data indicate that different membrane ubiquitin ligases are spatially sorted within the ER-nuclear envelope membrane system and that this differential localization contributes to their specificity...- Disulfide engineering to map subunit interactions in the proteasome and other macromolecular complexesMark Hochstrasser
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA
Methods Mol Biol 832:349-62. 2012.... 
Origin and function of ubiquitin-like proteinsMark Hochstrasser
Yale University, Department of Molecular Biophysics and Biochemistry, 266 Whitney Avenue, PO Box 208114, New Haven, Connecticut 06520, USA
Nature 458:422-9. 2009....- Modification of proteins by ubiquitin and ubiquitin-like proteinsOliver Kerscher
Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
Annu Rev Cell Dev Biol 22:159-80. 2006..The primary aim of this review is to summarize the latest developments in our understanding of the different Ubl-protein modification systems, including the shared and unique features of these related pathways... - Lingering mysteries of ubiquitin-chain assemblyMark Hochstrasser
Yale University, Department of Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA
Cell 124:27-34. 2006..Deciphering them will shed light on why substrates differ in the extent and timing of polyubiquitin modification and how ancillary ubiquitination factors function... - Ubiquitin ligation without a ligaseMark Hochstrasser
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
Dev Cell 13:4-6. 2007..An article in Molecular Cell (Hoeller et al., 2007) now describes the E3-independent monoubiquitination of certain proteins. The mechanism has interesting parallels to SUMO ligation... - Molecular biology. New proteases in a ubiquitin stewMark Hochstrasser
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Science 298:549-52. 2002 - SP-RING for SUMO: new functions bloom for a ubiquitin-like proteinM Hochstrasser
Yale University, Department of Molecular Biophysics and Biochemistry, 266 Whitney Avenue, New Haven, CT 06520, USA
Cell 107:5-8. 2001..Three groups now describe related E3-like factors that enhance transfer of SUMO to specific proteins. This family of factors includes proteins important for chromosome condensation, signal transduction, and ion channel biogenesis... - Biochemistry. All in the ubiquitin familyM Hochstrasser
Yale University, Department of Molecular Biophysics and Biochemistry, 266 Whitney Avenue, New Haven, CT 06520, USA
Science 289:563-4. 2000..In a comprehensive Perspective, Hochstrasser brings us up to date with the many new members of the ubiquitin modifier family and their multitudinous and diverse protein targets... - Evolution and function of ubiquitin-like protein-conjugation systemsM Hochstrasser
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA
Nat Cell Biol 2:E153-7. 2000..Newly discovered parallels between the activation of ubiquitin and the biosynthesis of certain enzyme cofactors now hint at the possible evolutionary origins of the ubiquitin system... - Desumoylation of the endoplasmic reticulum membrane VAP family protein Scs2 by Ulp1 and SUMO regulation of the inositol synthesis pathwayRachael Felberbaum
Departments of Molecular, Cell, and Developmental Biology, Yale University, New Haven, Connecticut, USA
Mol Cell Biol 32:64-75. 2012..These results provide the first evidence of cross-regulation between the SUMO and inositol pathways, including the sumoylation of an ER membrane protein central to phospholipid synthesis and phosphoinositide signaling... - The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathwaysA Y Amerik
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
Mol Biol Cell 11:3365-80. 2000.... - Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiaeA Y Amerik
Yale University, Department of Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA
Biol Chem 381:981-92. 2000..The data suggest that the DOA4 locus underwent a duplication after the divergence of K. lactis and S. cerevisiae. This information will facilitate fine-structure analysis of the Doa4 protein to help delineate its key functional elements... - Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI)Stefan G Kreft
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
J Biol Chem 281:4646-53. 2006..Finally, we provide evidence that the likely human Doa10 ortholog, TEB4 (MARCH-VI), adopts a topology similar to that of Doa10... - Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiaeJ Thomas Hannich
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA
J Biol Chem 280:4102-10. 2005..The results point to a surprisingly broad array of cellular processes regulated by SUMO conjugation and provide a starting point for detailed studies of how SUMO ligation contributes to these different regulatory mechanisms... - Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residueTommer Ravid
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Nat Cell Biol 9:422-7. 2007..The polyubiquitin chain can also be transferred to a lysine side chain, suggesting a mechanism for polyubiquitin chain assembly that precedes substrate modification... 
The Ulp1 SUMO isopeptidase: distinct domains required for viability, nuclear envelope localization, and substrate specificityShyr Jiann Li
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
J Cell Biol 160:1069-81. 2003..These data define key functional elements of Ulp1 and strongly suggest that subcellular localization is a physiologically significant constraint on SUMO isopeptidase specificity...- Analysis of protein ubiquitinationJeffrey D Laney
Yale University, New Haven, Connecticut, USA
Curr Protoc Protein Sci . 2002..These methods are suitable for a variety of eukaryotic cells, but techniques are specifically described for use with yeast and mammalian cells... - Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type IILin Wang
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA
Hepatology 48:1558-69. 2008..Furthermore, we present evidence that G982R weakly associates with various components of the ER quality control system. These data together demonstrate that the PFIC II mutants except R1153C and DeltaGly are degraded by the ERAD pathway... - The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylationYang Xie
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520 8114, USA
J Biol Chem 282:34176-84. 2007..Our data reveal a novel mechanism of substrate targeting in which sumoylation of a protein can help trigger its subsequent ubiquitination by recruiting a SUMO-binding ubiquitin ligase... - An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machineryMaria Francisca Arteaga
Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520 8026, USA
Proc Natl Acad Sci U S A 103:11178-83. 2006.... - Membrane and soluble substrates of the Doa10 ubiquitin ligase are degraded by distinct pathwaysTommer Ravid
Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
EMBO J 25:533-43. 2006..Thus, while Doa10 ubiquitinates both membrane and soluble proteins, the mechanisms of subsequent proteasome targeting differ... - A nuclear envelope protein linking nuclear pore basket assembly, SUMO protease regulation, and mRNA surveillanceAlaron Lewis
Departments of Cell Biology, Yale University, New Haven, CT 06520, USA
J Cell Biol 178:813-27. 2007..The results raise the possibility that NPC-localized protein desumoylation may be a key regulatory event preventing inappropriate pre-mRNA export... - The short-lived Matalpha2 transcriptional repressor is protected from degradation in vivo by interactions with its corepressors Tup1 and Ssn6Jeffrey D Laney
Department of Molecular Biophysics and Biochemistry, Brown University, Providence, RI 02912, USA
Mol Cell Biol 26:371-80. 2006..From these results, we propose that the fraction of alpha2 found in active regulatory complexes with Tup1 and Ssn6 is spared from rapid proteolytic destruction and is stabilized relative to the uncomplexed pool of the protein... - Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assemblyRobert J Tomko
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520 8114, USA
Mol Cell 38:393-403. 2010..Finally, the ATPase ring structure casts light on alternative RP structural models and the mechanism of RP action... - The Ulp2 SUMO protease is required for cell division following termination of the DNA damage checkpointDavid C Schwartz
Department of Molecular Biophysics, Yale University, New Haven, CT 06520 8114, USA
Mol Cell Biol 27:6948-61. 2007.... - A multimeric assembly factor controls the formation of alternative 20S proteasomesAndrew R Kusmierczyk
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520 8114, USA
Nat Struct Mol Biol 15:237-44. 2008..Our data demonstrate that Pba3-Pba4 orchestrates formation of a specific type of proteasome, the first example of a trans-acting factor that controls assembly of alternative proteasomal complexes... - beta-Subunit appendages promote 20S proteasome assembly by overcoming an Ump1-dependent checkpointXia Li
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
EMBO J 26:2339-49. 2007..We propose that dimerization is normally driven by the beta5 propeptide, an intramolecular chaperone, but beta7 addition overcomes an Ump1-dependent assembly checkpoint and stabilizes the precursor dimer... - Essential role of nuclear localization for yeast Ulp2 SUMO protease functionMary B Kroetz
Department of Cell Biology, Yale University, New Haven, CT 06520 8114, USA
Mol Biol Cell 20:2196-206. 2009.... - Small epitope-linker modules for PCR-based C-terminal tagging in Saccharomyces cerevisiaeMinoru Funakoshi
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
Yeast 26:185-92. 2009..The set of plasmids has been deposited in the non-profit plasmid repository Addgene (http://www.addgene.org)... - Assaying protein ubiquitination in Saccharomyces cerevisiaeJeffrey D Laney
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
Methods Enzymol 351:248-57. 2002 - Ubiquitin-dependent degradation of the yeast Mat(alpha)2 repressor enables a switch in developmental stateJeffrey D Laney
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA
Genes Dev 17:2259-70. 2003..Analogous epigenetic mechanisms for reprogramming transcription are likely to operate in many developmental pathways... - SUMO-independent in vivo activity of a SUMO-targeted ubiquitin ligase toward a short-lived transcription factorYang Xie
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
Genes Dev 24:893-903. 2010..We suggest that alpha2, and presumably other proteins, have surface features that mimic SUMO, and therefore can directly recruit STUbLs without prior SUMO conjugation... - Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle baseMinoru Funakoshi
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520 8114, USA
Cell 137:887-99. 2009..Our results demonstrate that proteasomal RP biogenesis requires multiple, functionally overlapping chaperones and suggest a model in which subunits form specific subcomplexes that then assemble into the base... - Plasticity in eucaryotic 20S proteasome ring assembly revealed by a subunit deletion in yeastIrina Velichutina
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA
EMBO J 23:500-10. 2004..Importantly, biogenesis of proteasomes is delayed at an early stage in pre9Delta cells, suggesting an advantage for Pre9 over Pre6 incorporation at the alpha3 position that facilitates correct assembly... - NF-kappaB signaling: flipping the switch with polyubiquitin chainsTommer Ravid
Yale University, Department of Molecular Biophysics and Biochemistry, 266 Whitney Avenue, P.O. Box 208114 New Haven, Connecticut 06520-8114, USA
Curr Biol 14:R898-900. 2004..Protein modification by ubiquitin has emerged as an important cellular regulatory mechanism. Recent studies illustrate the surprising ways in which polyubiquitin chains are manipulated in the regulation of NF-kappaB signaling... - Ulp2 and the DNA damage response: desumoylation enables safe passage through mitosisRachael Felberbaum
Department of Molecular, Cell, and Developmental Biology, Yale University, New Haven, Connecticut, USA
Cell Cycle 7:52-6. 2008.... - Mechanism and function of deubiquitinating enzymesAlexander Y Amerik
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, PO Box 208114, New Haven, CT 06520 8114, USA
Biochim Biophys Acta 1695:189-207. 2004..We also discuss briefly some of the proteases that act on ubiquitin-like protein (UBL) conjugates and compare them to DUBs... - Some assembly required: dedicated chaperones in eukaryotic proteasome biogenesisAndrew R Kusmierczyk
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
Biol Chem 389:1143-51. 2008.... - Identification of SUMO-interacting proteins by yeast two-hybrid analysisMary B Kroetz
Department of Cell Biology, Yale University, New Haven, CT, USA
Methods Mol Biol 497:107-20. 2009..Sumoylation can be verified by independent methods, such as a SUMO mobility shift assay. Finally, the chapter will compare the two-hybrid approach with mass spectrometric analysis as a means of identifying SUMO-interacting proteins... - Varshavsky's contributionsWolfgang Baumeister
Science 306:1290-2. 2004 - Ubiquitin signalling: what's in a chain?Mark Hochstrasser
Nat Cell Biol 6:571-2. 2004 - Diversity of degradation signals in the ubiquitin-proteasome systemTommer Ravid
Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem, Israel
Nat Rev Mol Cell Biol 9:679-90. 2008.... - Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal proteinGregory Huyer
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 279:38369-78. 2004.... - Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the proteasome regulatory particle that enhances proteasome stabilityMinoru Funakoshi
Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3 1 1, Higashi ku, Fukuoka 812 8582, Japan
J Cell Sci 117:6447-54. 2004..Our data suggest a potential mechanism for this protein-protein stabilization and also suggest that an intact proteasomal regulatory particle is required for responses to DNA damage... - A conserved late endosome-targeting signal required for Doa4 deubiquitylating enzyme functionAlexander Amerik
Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030, USA
J Cell Biol 175:825-35. 2006..This is the first demonstration of a physiologically important DUB subcellular localization signal and provides a striking example of the functional diversification of DUB paralogues by the evolution of alternative spatial signals... - Preparation and characterization of yeast and human desumoylating enzymesShyr-Jiann Li
Celera, South San Francisco, CA 94020, USA
Methods Enzymol 398:457-67. 2005 - Rtt106p is a histone chaperone involved in heterochromatin-mediated silencingShengbing Huang
Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Proc Natl Acad Sci U S A 102:13410-5. 2005..Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p. These biochemical and genetic data indicate that Rtt106p is a previously uncharacterized histone chaperone connecting S phase to epigenetic inheritance... - Ubiquitin-dependent control of development in Saccharomyces cerevisiaeJeffrey D Laney
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Box G J2, Providence, Rhode Island 02912, USA
Curr Opin Microbiol 7:647-54. 2004....
Research Grants
- DEGRADATION OF SHORT-LIVED REGULATORY PROTEINS IN YEASTMark Hochstrasser; Fiscal Year: 2007..abstract_text> ..
- FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMESMark Hochstrasser; Fiscal Year: 2007..4. Determine the molecular basis for the differences in specificity and activiity between the Ulpl and U|p2 desumoylating enzymes. ..
- PREDOCTORAL PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYMark Hochstrasser; Fiscal Year: 2007..D. training. Teaching experience is an essential part of training and all students teach with supervision and guidance from the faculty. The average time to graduation is 6 years. ..
- FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMESMark Hochstrasser; Fiscal Year: 2009..This project aims to deepen our understanding of the enzymes that detach certain ubiquitin-like proteins from their partners, with the long-term goal of developing therapies to treat patients suffering from cancer and other diseases. ..
- Function and Assembly of Eukaryotic ProteasomeMark Hochstrasser; Fiscal Year: 2010..A potential RP assembly factor recently discovered in the PI's laboratory provides the starting point for these studies. ..
- FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMESMark Hochstrasser; Fiscal Year: 2003....
- DEGRADTION OF SHORT-LIVED REGULATORY PROTEINS IN YEASTMark Hochstrasser; Fiscal Year: 2004..Aim 4. Continue structure-function studies on the yeast 20S proteasome and assess its interactions with the l9S regulatory complex. ..
- FUNCTIONS AND MECHANISMS OF DEUBIQUITINATING ENZYMESMark Hochstrasser; Fiscal Year: 2010..This project aims to deepen our understanding of the enzymes that detach certain ubiquitin-like proteins from their partners, with the long-term goal of developing therapies to treat patients suffering from cancer and other diseases. ..