Abstract
Stimulation of cells with tumor necrosis factor (TNFα) triggers a recruitment of various signaling molecules, such as RIP, to the TNFα receptor 1 complex, leading to activation of NF-κB. Previous studies indicate that RIP plays an essential role for TNFα-induced NF-κB activation, but the molecular mechanism by which RIP mediates TNFα signals to activate NF-κB is not fully defined. Earlier studies suggest that RIP undergoes a ligand-dependent ubiquitination. However, it remains to be determined whether the ubiquitination of RIP is required for TNFα-induced NF-κB activation. In this study, we have identified Lys377 of RIP as the functional ubiquitination site, because mutating this residue to arginine completely abolished RIP-mediated NF-κB activation. The K377R mutation of RIP cannot undergo ligand-dependent ubiquitination and fails to recruit its downstream signaling components into the TNFα receptor 1 complex. Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFα-induced NF-κB activation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 13636-13643 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 281 |
| Issue number | 19 |
| DOIs | |
| State | Published - May 12 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
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Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation. / Li, Hongxiu; Kobayashi, Masayuki; Blonska, Marzenna; You, Yun; Lin, Xin.
In: Journal of Biological Chemistry, Vol. 281, No. 19, 12.05.2006, p. 13636-13643.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation
AU - Li, Hongxiu
AU - Kobayashi, Masayuki
AU - Blonska, Marzenna
AU - You, Yun
AU - Lin, Xin
PY - 2006/5/12
Y1 - 2006/5/12
N2 - Stimulation of cells with tumor necrosis factor (TNFα) triggers a recruitment of various signaling molecules, such as RIP, to the TNFα receptor 1 complex, leading to activation of NF-κB. Previous studies indicate that RIP plays an essential role for TNFα-induced NF-κB activation, but the molecular mechanism by which RIP mediates TNFα signals to activate NF-κB is not fully defined. Earlier studies suggest that RIP undergoes a ligand-dependent ubiquitination. However, it remains to be determined whether the ubiquitination of RIP is required for TNFα-induced NF-κB activation. In this study, we have identified Lys377 of RIP as the functional ubiquitination site, because mutating this residue to arginine completely abolished RIP-mediated NF-κB activation. The K377R mutation of RIP cannot undergo ligand-dependent ubiquitination and fails to recruit its downstream signaling components into the TNFα receptor 1 complex. Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFα-induced NF-κB activation.
AB - Stimulation of cells with tumor necrosis factor (TNFα) triggers a recruitment of various signaling molecules, such as RIP, to the TNFα receptor 1 complex, leading to activation of NF-κB. Previous studies indicate that RIP plays an essential role for TNFα-induced NF-κB activation, but the molecular mechanism by which RIP mediates TNFα signals to activate NF-κB is not fully defined. Earlier studies suggest that RIP undergoes a ligand-dependent ubiquitination. However, it remains to be determined whether the ubiquitination of RIP is required for TNFα-induced NF-κB activation. In this study, we have identified Lys377 of RIP as the functional ubiquitination site, because mutating this residue to arginine completely abolished RIP-mediated NF-κB activation. The K377R mutation of RIP cannot undergo ligand-dependent ubiquitination and fails to recruit its downstream signaling components into the TNFα receptor 1 complex. Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFα-induced NF-κB activation.
UR - http://www.scopus.com/inward/record.url?scp=33744951304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744951304&partnerID=8YFLogxK
U2 - 10.1074/jbc.M600620200
DO - 10.1074/jbc.M600620200
M3 - Article
C2 - 16543241
AN - SCOPUS:33744951304
VL - 281
SP - 13636
EP - 13643
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -