C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/62 (2006.01) C07K 14/00 (2006.01) C07K 14/47 (2006.01) C07K 19/00 (2006.01) C12N 9/64 (2006.01) G01N 33/53 (2006.01)
Patent
CA 2483494
A C-terminally modified Ubiquitin (Ub) derivative, ubiquitin vinyl sulfone (UbVS), which is specific for deubiquitinating enzymes (DUBs), was synthesized as an active site directed probe that irreversibly modifies a subset of Ub C- terminal hydrolases (UCHs) and Ub specific processing proteases (UBPs), is provided [125I]-UbVS modifies 6 of the 17 known and putative yeast deubiquitinating enzymes, namely Yuh1p, Ubp1p, Ubp2p, Ubp6p, Ubp12p and Ubp15p. In mammalian cells, a greater number of polypeptides is labeled, most of which are DUBs. An additional DUB that associates with the mammalian 26S proteasome, novel protein USP14, a mammalian homolog of yeast Ubp6p that is bound to the proteasome, is provided.
La présente invention concerne un dérivé de l'ubiquitine (Ub) à extrémité C-terminale modifiée, l'ubiquitine vinylsulfone (UbVS), qui est spécifique des enzymes de désubiquitination (DUB) et qui a été synthétisée sous la forme d'une sonde dirigée contre un site actif, qui modifie de manière irréversible un sous-ensemble d'hydrolases à extrémité C-terminale Ub (UCH) et de protéases de maturation spécifiques Ub (UBP) [?125¿I]-. UbVS modifie 6 des 17 enzymes de désubiquitination de la levure connues et présumées, à savoir Yuh1p, Ubp1p, Ubp2p, Ubp6p, Ubp12p et Ubp15p. Dans les cellules mammaliennes, un plus grand nombre de polypeptides sont marqués, dont la plupart sont des DUB. L'invention se rapporte également à un DUB supplémentaire qui s'associe au protéasome 26S mammalien, une nouvelle protéine USP14, un homologue mammalien de l'Ubp6p de la levure qui est lié au protéasome.
Borodovsky Anna
Galardy Paul
Gan-Erdene Tudevin
Hemelaar Joris
Kessler Benedikt
Borodovsky Anna
Emory University
Galardy Paul
Gan-Erdene Tudevin
Hemelaar Joris
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