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The role of the ubiquitin system in human cytomegalovirus-mediated degradation of MHC class I heavy chains

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Citation

Hassink, G. C. (2006, May 22). The role of the ubiquitin system in human

cytomegalovirus-mediated degradation of MHC class I heavy chains. Retrieved from

https://hdl.handle.net/1887/4414

Version:

Corrected Publisher’s Version

License:

Licence agreement concerning inclusion of doctoral thesis in the

Institutional Repository of the University of Leiden

Downloaded from:

https://hdl.handle.net/1887/4414

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THE ROLE OF THE UBIQUITIN SYSTEM IN HUMAN CYTOMEGALOVIRUS-MEDIATED DEGRADATION OF

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THE ROLE OF THE UBIQUITIN SYSTEM IN HUMAN CYTOMEGALOVIRUS-MEDIATED DEGRADATION OF

MHC CLASS I HEAVY CHAINS

PROEFSCHRIFT

ter verkrijging van

de graad van Doctor aan de UniversiteitLeiden, op gezag van de Rector Magnificus Dr.D.D.Breimer,

hoogleraar in de faculteitder W iskunde en Natuurwetenschappen en die der Geneeskunde,

volgens besluitvan hetCollege voor Promoties te verdedigen op maandag 22 mei2006

te klokke 14.15 uur

door

Gerrit Cornelis Hassink

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Contents

Abbreviations 8

Chapter 1 Introduction.Partly published in Curr. Top. Microbiol.

Immunol. 1995, 300:57-94

9

Chapter 2 Rat Cytomegalovirus Induces a Temporal

Down-regulation of Major Histocompatibility Complex Class I CellSurface Expression.Vir. Immunol. 2005, 18:607-15

3 3

Chapter 3 Ubiquitination is essentialfor human cytomegalovirus

US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol.Biochem J. 2001, 358:369-77

4 9

Chapter 4 Human Hrd1 is an E3 ubiquitin ligase involved in

degradation of proteins from the Endoplasmic Reticulum.J.Biol.Chem. 2004, 279:3525-34

6 9

Chapter 5 TEB4 is a C4HC3 RING finger-containing ubiquitin

ligase of the endoplasmic reticulum.Biochem J. 2005, 388:647-55

95

Chapter 6 Ubiquitination of lysine residues within MHC class I

heavy chains is essentialfor dislocation by HCMV US2 but not by HCMV US11. Submitted

1 1 5

Chapter 7 Human cytomegalovirus-encoded US2 and US11 target

unassembled MHC class I heavy chains for degradation.Mol Immunol. 2006, 43:1258-66.

1 4 1

Chapter 8 MHC class I heavy chains are dislocated from the

endoplasmic reticulum to the cytosolin a vectorial fashion,commencing at the C-terminus.Submitted

1 5 9

Chapter 9 Summary and Discussion 1 81

Nederlandse samenvatting 2 0 1

Curriculum Vitae 2 1 1

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8 HC HCMV HLA IFN IL IRES kDa mAb MHC MOI NK cell NP40 PDI PE ProtK TAP TM TNF Tx-100 US wt ZL3H ZLVS heavy chain

human cytomegalovirus human leucocyte antigen interferon

interleukin

internalribosomalentry site kilodalton

monoclonalantibody

major histocompatibility complex multiplicity of infection.

naturalkiller cell nonidetP-40

protein disulfide isomerase phycoerythrin

proteinase K

transporter associated with antigen processing transmembrane

tumor necrosis factor triton X-100

unique short wild type

carboxybenzyl-leucyl-leucyl-leucinal

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