NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation

Fang, Difeng; He, Kun; Wang, Na; Sang, Zhihong; Qiu, Xiu; Xu, Guang; Jian, Zhao; Liu, Bing; Li, Tao; Li, Huiyan; Li, Ailing; Zhou, Tao; Gong, Weili; Yang, Baoli; Karin, Michael; Zhang, Xuemin; Li, Weihua

doi:10.1038/ncomms5513

Cited by 53 publications

(32 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conventional IPs were performed as previously described [10][11][12][13]. The denaturation IPs for detection of ubiquitination were performed according to the study by Fang, et al [14] with slight modifications, briefly, lysates from Bel-7402 cells under different treatment were prepared in Western/IP lysis buffer (Beyotime, Haimen, China). SDS was added into the supernatants of cell lysates to a final concentration 1%, noncovalently associated proteins were removed by boiling at 100°C for 10 min.…”

Section: Immunohistochemistry (Ihc) Immunefluorescence (If) and Wesmentioning

confidence: 99%

CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells

Tang

Chen

et al. 2015

Cellular Signalling

View full text Add to dashboard Cite

Section: Immunohistochemistry (Ihc) Immunefluorescence (If) and Wesmentioning

confidence: 99%

CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells

Tang

Chen

et al. 2015

Cellular Signalling

View full text Add to dashboard Cite

“…Proteins in the conditioned medium (5 ml) were concentrated by TCA precipitation. Concentrated protein samples were analyzed by SDS-PAGE and in-gel digestions were carried out as previously described [38]. The digested samples were analyzed by nanoLC-MS/MS (nanoACQUITY UPLC and SYNAPT G2 HD mass spectrometer; Waters).…”

Section: Mass Spectrometry Analysismentioning

confidence: 99%

Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration

et al. 2016

Self Cite

View full text Add to dashboard Cite

Necroptosis is a programmed, caspase-independent cell death that is morphologically similar to necrosis. TNF-induced necroptosis is mediated by receptor-interacting protein kinases, RIP1 and RIP3, and the mixed lineage kinase domain-like (MLKL). After being phosphorylated by RIP3, MLKL is translocated to the plasma membrane and mediates necroptosis. However, the execution of necroptosis and its role in inflammation and other cellular responses remain largely elusive. In this study, we report that MLKL-mediated activation of cell-surface proteases of the a disintegrin and metalloprotease (ADAM) family promotes necroptosis, inflammation and cell migration. ADAMs are specifically activated at the early stage of necroptosis when MLKL is phosphorylated and translocated to the cell plasma membrane. Activation of ADAMs induces ectodomain shedding of diverse cell-surface proteins including adhesion molecules, receptors, growth factors and cytokines. Importantly, the shedding of cell-surface proteins disrupts cell adhesion and accelerates necroptosis, while the soluble fragments of the cleaved proteins trigger the inflammatory responses. We also demonstrate that the shedding of E-cadherin ectodomain from necroptotic cells promotes cell migration. Thus, our study provides a novel mechanism of necroptosis-induced inflammation and new insights into the physiological and pathological functions of this unique form of cell death.

show abstract

“…Mice deficient in Nedd4 (Nedd4 −/− mice) were neonatal lethal, with delayed embryonic development and reduced growth and body weight due 20 . It has been found that Nedd4 plays an important role in immune cells including T cells 21 and B cells 22 , however, the physiological functions and molecular mechanism of Nedd4 in macrophages still need to be investigated.…”

Section: Introductionmentioning

confidence: 99%

E3 ubiquitin ligase Nedd4 inhibits AP-1 activity and TNF-α production through targeting p38α for polyubiquitination and subsequent degradation

Liu

Zhang

Gan

et al. 2017

Sci Rep

View full text Add to dashboard Cite

p38α plays an important role in many inflammatory diseases, such as skin inflammation, endotoxic shock and arthritis. Ubiquitination is a vital posttranslational modification of proteins and plays a crucial regulatory role in inflammatory cells. It has been reported that ubiquitination of Tak1 and TAB1 upstream of p38α can regulate p38α activation respectively. However, p38α ubiquitination is not yet clear. In this paper, we showed that E3 ubiquitin ligase Nedd4 is a regulatory component of the p38α pathway and is responsible for polyubiquitination of p38α through K48-linked and K63-linked polyubiquitination. The levels of p38α and its downstream target TNF-α were increased in Nedd4 deficient macrophages response to LPS compared with wild-type cells. AP-1 activity and degradation of p38α were induced by Nedd4 in a dose-dependent manner. Furthermore, we found that phosphorylation of p38α is involved in the interactions between p38α and Nedd4 and subsequently promotes polyubiquitination of p38α, especially K48-linked polyubiquitination by Nedd4. The different conformation of two p38α isoforms (p38αV1 and p38αV2) might be the cause of their different interactions with Nedd4 and their polyubiquitination sites by Nedd4. Thus, NEDD4 is a previously unknown component of the p38α signaling complex necessary for TNF-α activation.

show abstract

NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation

Cited by 53 publications

References 36 publications

CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells

CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells

Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration

E3 ubiquitin ligase Nedd4 inhibits AP-1 activity and TNF-α production through targeting p38α for polyubiquitination and subsequent degradation

Contact Info

Product

Resources

About