ISGylation of host protein filamin B

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
ISG15 negatively regulates the scaffold protein filamin B. In response to type I IFNs, filamin B recruits RAC1, MEKK1, and MKK4, enhancing their sequential activation and thereby promoting JNK activation and apoptosis. ISGylation of filamin B leads to the disassociation of RAC1, MEKK1, and MKK4 from the scaffold, preventing type I IFN dependent JNK activation and apoptosis. It has been suggested that this inhibition of apoptosis may protect uninfected bystander cells from IFN-mediated apoptosis (Jeon et al, 2009).
Literature References
PubMed ID Title Journal Year
16009940 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways

Denison, C, Krug, RM, Huibregtse, JM, Gygi, S, Zhao, C

Proc Natl Acad Sci U S A 2005
19270716 ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway

Yu, KR, Zhang, DE, Choi, JS, Bang, OS, Kim, KI, Oh, KH, Kim, SM, Lee, JY, Jeon, YJ, Ka, SH, Chung, CH

EMBO Rep 2009
12582176 High-throughput immunoblotting. Ubiquitiin-like protein ISG15 modifies key regulators of signal transduction

Malakhova, OA, Malakhov, MP, Zhang, DE, Jacobs, BS, Borden, EC, Kim, KI

J Biol Chem 2003
Catalyst Activity

ubiquitin-protein transferase activity of ISG15:UBCH8:ISG15 E3 ligase [cytosol]

Orthologous Events
Cite Us!