WILLIAM SKACH

Summary

Affiliation: Oregon Health and Science University
Country: USA

Publications

  1. pmc The expanding role of the ER translocon in membrane protein folding
    William R Skach
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97239, USA
    J Cell Biol 179:1333-5. 2007
  2. pmc Mechanisms of CFTR Folding at the Endoplasmic Reticulum
    Soo Jung Kim
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University Portland, OR, USA
    Front Pharmacol 3:201. 2012
  3. pmc Cellular mechanisms of membrane protein folding
    William R Skach
    William R Skach is in the Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon, USA
    Nat Struct Mol Biol 16:606-12. 2009
  4. ncbi request reprint CFTR: new members join the fold
    William R Skach
    Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97239, USA
    Cell 127:673-5. 2006
  5. ncbi request reprint Defects in processing and trafficking of the cystic fibrosis transmembrane conductance regulator
    W R Skach
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, USA
    Kidney Int 57:825-31. 2000
  6. ncbi request reprint Molecular mechanism of P-glycoprotein assembly into cellular membranes
    Victoria Anthony
    Division of Molecular Medicine, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97201, USA
    Curr Protein Pept Sci 3:485-501. 2002
  7. ncbi request reprint An energy-dependent maturation step is required for release of the cystic fibrosis transmembrane conductance regulator from early endoplasmic reticulum biosynthetic machinery
    Jon Oberdorf
    Department of Biochemistry and Moleculor Biology, Oregon Health and Sciences University, Portland, Oregon 97239, USA
    J Biol Chem 280:38193-202. 2005
  8. ncbi request reprint Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum Sec61 translocon
    David Pitonzo
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University Portland, Oregon, 3181 SW Sam Jackson Park Rd L 224 Portland, Oregon 97239, USA
    Biochim Biophys Acta 1758:976-88. 2006
  9. ncbi request reprint Cooperativity and flexibility of cystic fibrosis transmembrane conductance regulator transmembrane segments participate in membrane localization of a charged residue
    Kristin Carveth
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, Oregon 97201, USA
    J Biol Chem 277:39507-14. 2002
  10. ncbi request reprint Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein
    Heather Sadlish
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon 97239, USA
    Nat Struct Mol Biol 12:870-8. 2005

Research Grants

Collaborators

  • Arthur E Johnson
  • J Frydman
  • JEFFREY BRODSKY
  • David Pitonzo
  • Teresa M Buck
  • Jon Oberdorf
  • Eric J Carlson
  • Toru Shibatani
  • Soo Jung Kim
  • Fei Fei Yan
  • Colin J Daniel
  • Victoria Anthony
  • Larry L David
  • Judit Wahlman
  • Dennis J Chia
  • Ashley L McCormack
  • Eric Carlson
  • Heather Sadlish
  • Stephanie A Etchells
  • Kristin Carveth
  • Pei Chun Chen
  • Fang Wang
  • Show Ling Shyng
  • Emily B Pratt
  • Yoshihiro Matsumura
  • Zhongying Yang
  • Brian Conti
  • Neil J Bulleid
  • Justin Wagner
  • Steven Grund
  • George N Demartino
  • Peter Rotwein
  • Fredrick Larabee
  • Ujwal Shinde
  • Vivian Hwa
  • Klaus Fruh
  • Ron G Rosenfeld
  • Ezhilkani Subbian
  • Anne Roobol
  • Alice Y Yam
  • Martin J Carden
  • Nathan Bays
  • Anne S Meyer
  • Klaus Frueh
  • Yiwei Miao
  • Yuanlong Shao
  • Larry David
  • Joel Eledge
  • Teresa Buck

Detail Information

Publications26

  1. pmc The expanding role of the ER translocon in membrane protein folding
    William R Skach
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97239, USA
    J Cell Biol 179:1333-5. 2007
    ..These surprising findings support an expanded role for the translocon in membrane protein biogenesis and require reassessment of current views based on a single small functional pore...
  2. pmc Mechanisms of CFTR Folding at the Endoplasmic Reticulum
    Soo Jung Kim
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University Portland, OR, USA
    Front Pharmacol 3:201. 2012
    ....
  3. pmc Cellular mechanisms of membrane protein folding
    William R Skach
    William R Skach is in the Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon, USA
    Nat Struct Mol Biol 16:606-12. 2009
    ....
  4. ncbi request reprint CFTR: new members join the fold
    William R Skach
    Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97239, USA
    Cell 127:673-5. 2006
    ..Among the proteins interacting with CFTR is a new member of the Hsp90 chaperone system, Aha1, that plays a central role in CFTR folding...
  5. ncbi request reprint Defects in processing and trafficking of the cystic fibrosis transmembrane conductance regulator
    W R Skach
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, USA
    Kidney Int 57:825-31. 2000
    ..Understanding how cellular machinery mediates this process will be an important step in designing strategies to modify protein folding and degradation in CF and related ion channelopathies...
  6. ncbi request reprint Molecular mechanism of P-glycoprotein assembly into cellular membranes
    Victoria Anthony
    Division of Molecular Medicine, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97201, USA
    Curr Protein Pept Sci 3:485-501. 2002
    ....
  7. ncbi request reprint An energy-dependent maturation step is required for release of the cystic fibrosis transmembrane conductance regulator from early endoplasmic reticulum biosynthetic machinery
    Jon Oberdorf
    Department of Biochemistry and Moleculor Biology, Oregon Health and Sciences University, Portland, Oregon 97239, USA
    J Biol Chem 280:38193-202. 2005
    ....
  8. ncbi request reprint Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum Sec61 translocon
    David Pitonzo
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University Portland, Oregon, 3181 SW Sam Jackson Park Rd L 224 Portland, Oregon 97239, USA
    Biochim Biophys Acta 1758:976-88. 2006
    ..AQP biogenesis thus has wide ranging implications for mechanisms of translocon function and general membrane protein folding pathways...
  9. ncbi request reprint Cooperativity and flexibility of cystic fibrosis transmembrane conductance regulator transmembrane segments participate in membrane localization of a charged residue
    Kristin Carveth
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, Oregon 97201, USA
    J Biol Chem 277:39507-14. 2002
    ....
  10. ncbi request reprint Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein
    Heather Sadlish
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, Oregon 97239, USA
    Nat Struct Mol Biol 12:870-8. 2005
    ..This mechanism provides a means to facilitate early folding events before release into the lipid bilayer...
  11. pmc Control of translocation through the Sec61 translocon by nascent polypeptide structure within the ribosome
    Colin J Daniel
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239, USA
    J Biol Chem 283:20864-73. 2008
    ....
  12. ncbi request reprint In vitro reconstitution of CFTR biogenesis and degradation
    Jon Oberdorf
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, OR, USA
    Methods Mol Med 70:295-310. 2002
  13. pmc Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum Sec61 translocon
    David Pitonzo
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97239, USA
    Mol Biol Cell 20:685-98. 2009
    ..These findings contrast with passive partitioning models and indicate that Sec61alpha can retain TMs and actively inhibit membrane integration in a sequence-specific and ATP-dependent manner...
  14. pmc Pharmacological chaperoning: two 'hits' are better than one
    William R Skach
    Department of Biochemistry and Molecular Biology, 3181 SW Sam Jackson Park Road, MC L224, Oregon Health and Sciences University, Portland, OR 97239, U S A
    Biochem J 406:e1-2. 2007
    ..These findings raise the intriguing possibility that corrector molecules acting at different steps along the folding pathway might provide a multidrug approach to human protein folding disorders...
  15. pmc Global organization and function of mammalian cytosolic proteasome pools: Implications for PA28 and 19S regulatory complexes
    Toru Shibatani
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97201, USA
    Mol Biol Cell 17:4962-71. 2006
    ....
  16. pmc p97 functions as an auxiliary factor to facilitate TM domain extraction during CFTR ER-associated degradation
    Eric J Carlson
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, 97239, USA
    EMBO J 25:4557-66. 2006
    ..Thus, we propose that p97 functions in ERAD as a nonessential but important ancillary component to the proteasome where it facilitates substrate presentation and increases the degradation rate and efficiency of stable (TM) domains...
  17. ncbi request reprint Differential stability of biogenesis intermediates reveals a common pathway for aquaporin-1 topological maturation
    Teresa M Buck
    Molecular Medicine Division, Department of Medicine, Oregon Health Sciences University, Portland, Oregon 97201, USA
    J Biol Chem 280:261-9. 2005
    ....
  18. ncbi request reprint Uncoupling proteasome peptidase and ATPase activities results in cytosolic release of an ER polytopic protein
    Jon Oberdorf
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    J Cell Sci 119:303-13. 2006
    ..Active site inhibitors reduce this capacity, uncouple ATPase and peptidase activities, and generate cytosolic degradation intermediates by allowing the rate of unfolding to exceed the rate of polypeptide cleavage...
  19. ncbi request reprint Evidence for stabilization of aquaporin-2 folding mutants by N-linked glycosylation in endoplasmic reticulum
    Teresa M Buck
    Molecular Medicine Division, Department of Medicine, Oregon Health Sciences University, Portland, Oregon 97239, USA
    Am J Physiol Cell Physiol 287:C1292-9. 2004
    ..These results suggest that addition of a single N-linked oligosaccharide moiety can partially compensate for ER folding defects induced by disease-related mutations...
  20. ncbi request reprint Reticulocyte lysate as a model system to study endoplasmic reticulum membrane protein degradation
    Eric Carlson
    Division of Molecular Medicine, Oregon Health Sciences University, Portland, USA
    Methods Mol Biol 301:185-205. 2005
    ..These techniques provide a powerful tool for dissecting components involved in ubiquitination, degradation, and in particular, extraction of transmembrane ERAD substrates...
  21. ncbi request reprint Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits
    Toru Shibatani
    Division of Molecular Medicine, Oregon Health and Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201, USA
    Biochemistry 44:5982-92. 2005
    ..Our results identify two potential new subunits of mammalian OST and demonstrate a remarkable heterogeneity in OST composition that may reflect a means for controlling nascent chain glycosylation...
  22. pmc Role of Hsp90 in biogenesis of the beta-cell ATP-sensitive potassium channel complex
    Fei Fei Yan
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Mol Biol Cell 21:1945-54. 2010
    ..Our study demonstrates that Hsp90 regulates biogenesis efficiency of heteromeric K(ATP) channels via SUR1, thereby affecting functional expression of the channel in beta-cell membrane...
  23. ncbi request reprint Aberrant folding of a mutant Stat5b causes growth hormone insensitivity and proteasomal dysfunction
    Dennis J Chia
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 281:6552-8. 2006
    ..The potential for aggregation and formation of cytoplasmic inclusions raises the possibility that Stat5bA630P could produce additional defects through inhibition of proteasome function...
  24. ncbi request reprint A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization
    Teresa M Buck
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, USA
    Nat Struct Mol Biol 14:762-9. 2007
    ..These findings suggest a general mechanism by which evolutionary divergence of membrane proteins can confer new functional properties via alternative folding pathways that give rise to a common final structure...
  25. pmc Real-time fluorescence detection of ERAD substrate retrotranslocation in a mammalian in vitro system
    Judit Wahlman
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843, USA
    Cell 129:943-55. 2007
    ..In addition, pro-alpha factor photocrosslinked derlin-1, but not Sec61alpha. Thus, derlin-1 appears to be involved in pro-alpha factor retrotranslocation...
  26. ncbi request reprint The cotranslational contacts between ribosome-bound nascent polypeptides and the subunits of the hetero-oligomeric chaperonin TRiC probed by photocross-linking
    Stephanie A Etchells
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843, USA
    J Biol Chem 280:28118-26. 2005
    ..We conclude that elongating actin and luciferase nascent chains contact multiple TRiC subunits upon emerging from the ribosome, and that the TRiC subunits contacted by nascent actin change as it elongates and starts to fold...

Research Grants20

  1. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 1999
    ..This work will provide a detailed understanding of cellular mechanisms which regulate polytopic protein assembly and allow further investigation into how these pathways might be disrupted in acquired or inherited human diseases. ..
  2. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 1999
    ..Identification of specific cellular proteins involved in this process will provide new potential targets for therapy of CF and other human diseases in which protein trafficking is involved. ..
  3. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2005
    ..Results of these studies will provide a major advance in our understanding of normal and pathological mechanisms of polytopic protein folding. ..
  4. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2006
    ..Results of these studies will provide a major advance in our understanding of normal and pathological mechanisms of polytopic protein folding. ..
  5. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2007
    ..Results of these studies will provide a major advance in our understanding of normal and pathological mechanisms of polytopic protein folding. ..
  6. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2009
    ....
  7. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    William R Skach; Fiscal Year: 2010
    ....
  8. Mechanisms of Polyptopic Protein Biogenesis in the ER
    William R Skach; Fiscal Year: 2010
    ....
  9. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2004
    ....
  10. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2004
    ..abstract_text> ..
  11. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2000
    ..Identification of specific cellular proteins involved in this process will provide new potential targets for therapy of CF and other human diseases in which protein trafficking is involved. ..
  12. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2001
    ..abstract_text> ..
  13. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2001
    ....
  14. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2002
    ..abstract_text> ..
  15. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2002
    ....
  16. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    WILLIAM SKACH; Fiscal Year: 2003
    ..abstract_text> ..
  17. MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ER
    WILLIAM SKACH; Fiscal Year: 2003
    ....
  18. BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTR
    William R Skach; Fiscal Year: 2010
    ..abstract_text> ..