Proteomic identification of proteins conjugated to ISG15 in mouse and human cells.

Article Details


Giannakopoulos NV, Luo JK, Papov V, Zou W, Lenschow DJ, Jacobs BS, Borden EC, Li J, Virgin HW, Zhang DE

Proteomic identification of proteins conjugated to ISG15 in mouse and human cells.

Biochem Biophys Res Commun. 2005 Oct 21;336(2):496-506.

PubMed ID
16139798 [ View in PubMed

Though the interferon-inducible protein ISG15 was one of the first ubiquitin-like modifiers to be discovered, much remains unknown about the identity of proteins conjugated to ISG15 or the biologic consequences of modification. To gain a better understanding of the cellular pathways affected by ISG15, we identified proteins targeted for ISGylation using a proteomic approach. Mass spectrometric analysis identified 76 candidate ISGylation targets in anti-ISG15 immunoprecipitates from interferon-treated mouse or human cells. Twenty-one proteins were found in both mouse and human samples, including STAT1, a known target of ISGylation. Candidates identified in both species were tested for ISGylation in a transfection system: 18 of 19 proteins tested were ISGylated in this system. Two candidates, EF-2 and VCP, were also shown to be ISGylated in an interferon-dependent manner in the absence of exogenous over-expression. Seven proteins identified from a single species, but functionally related to candidates found in both species, were also ISGylated in the over-expression system. Proteins that can be ISGylated play important roles in translation, glycolysis, stress responses, and cell motility. These data indicate that ISGylation targets proteins found in several fundamentally important cellular pathways and will contribute to understanding the physiologic role of interferon-induced ISG15 and ISG15 conjugation.

DrugBank Data that Cites this Article

NameUniProt ID
Pyruvate kinase PKMP14618Details
Threonine--tRNA ligase, cytoplasmicP26639Details
Alanine--tRNA ligase, cytoplasmicP49588Details
L-lactate dehydrogenase A chainP00338Details
Malate dehydrogenase, cytoplasmicP40925Details
Heat shock protein HSP 90-alphaP07900Details
Annexin A2P07355Details
Glucose-6-phosphate isomeraseP06744Details
Heat shock protein HSP 90-betaP08238Details
Heat shock cognate 71 kDa proteinP11142Details
Elongation factor 2P13639Details
Elongation factor 1-alpha 1P68104Details
Transitional endoplasmic reticulum ATPaseP55072Details
Ubiquitin-like modifier-activating enzyme 1P22314Details
Actin, cytoplasmic 1P60709Details
ATP-citrate synthaseP53396Details
Signal transducer and activator of transcription 1-alpha/betaP42224Details