NOTCH signaloinnista ja SARS2 interaktioproteiineista

SARS2 ORF8 interaktioproteiinit ovat POGLUT2 ja POGLUT3,
POFUT1 . katso alla olevaa kuvaa. Se on hiirellä tehty tutkimus.

https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13251@10.1002/(ISSN)1873-3468.reviews
Review Article

Free Access

Multiple roles for O‐glycans in Notch signalling

Shweta Varshney

Pamela Stanley

First published: 12 September 2018

https://doi.org/10.1002/1873-3468.13251

Notch signalling regulates a plethora of developmental processes and is also essential for the maintenance of tissue homeostasis in adults. Therefore, fine‐tuning of Notch signalling strength needs to be tightly regulated. Of key importance for the regulation of Notch signalling are O‐fucose, O‐GlcNAc and O‐glucose glycans attached to the extracellular domain of Notch receptors. The EGF repeats of the Notch receptor extracellular domain harbour consensus sites for addition of the different types of O‐glycan to Ser or Thr, which takes place in the endoplasmic reticulum. Studies from Drosophila to mammals have demonstrated the multifaceted roles of O‐glycosylation in regulating Notch signalling. O‐glycosylation modulates different aspects of Notch signalling including recognition by Notch ligands, the strength of ligand binding, Notch receptor trafficking, stability and activation at the cell surface. Defects in O‐glycosylation of Notch receptors give rise to pathologies in humans. This Review summarizes the nature of the O‐glycans on Notch receptors and their differential effects on Notch signalling.

Abbreviations

ADAM , a disintegrin and metalloprotease
ANK , Ankyrin repeats
AOS4 , Adams‐Oliver syndrome 4
C2 domain , module at the N‐terminus of Notch ligands
CHO , Chinese hamster ovary
CSL , CBF‐1 suppressor of hairless‐LAG1
DDD , Dowling‐Degos disease
DLL , Delta‐like
EGF , epidermal growth factor‐like
EOGT , EGF‐domain‐specific O‐GlcNAc
ER , endoplasmic reticulum
ES , embryonic stem cells
Gal , galactose
GDP‐Fuc , GDP‐fucose
GlcNAc , N ‐acetylglucosamine
GSI , gamma‐secretase inhibitor
GXYLT1 , glucoside xylosyltransferase 1
GXYLT2 , glucoside xylosyltransferase 2
HD , heterodimerization domain
HEK , human embryonic kidney
HSC , haematopoietic stem cells
HS‐DDD4 , hidradenitis suppurativa‐Dowling‐Degos disease 4
JAG1 , Jagged 1
LFNG , Lunatic fringe
LGMD2Z , limb‐girdle muscular dystrophy type 2Z
MAML , mastermind‐like
MFNG , Manic fringe
NECD , Notch extracellular domain
NeuAc , N ‐acetylneuraminic acid
NEXT , Notch extracellular truncation
NICD , Notch intracellular domain
NRR , negative regulatory region
POFUT1 , protein O‐fucosyltransferase 1  ( =SARS2 interaction protein)
POGLUT1 , Protein O‐glucosyltransferase 1
RAM , RBP‐Jκ‐associated module
RFNG , Radical fringe
SCDO3 , spondylocostal dysostosis 3
Su(H) , suppressor of hairless
TAD , transcriptional activation domain
U2OS , human osteosarcoma cell line
XXYLT1 , xylose xylosyltransferase 1 

  

 

Representation of mouse NOTCH1 extracellular domain depicting EGF repeats with different O‐glycan consensus sites that may be modified with the O‐glycans shown. One of the EGF domains is magnified to show the consensus site for each type of O‐glycan. Different O‐glycans, their respective differential extension with sugars (+/−), and the glycosyltransferases responsible for the transfer of each sugar are shown below the diagram. The transfer of O‐glucose by POGLUT2 or POGLUT3 occurs only on EGF11 in NOTCH1. The consensus site is between Cys³ and Cys⁴, indicated by the different location of the glucose symbol in EGF11 in the diagram.