IMPLICATION OF THE UBIQUITIN-PROTEASOME PATHWAY IN THE VEGF-DEPENDENT DOWN-REGULATION OF VEGFR-2 IN ENDOTHELIAL CELLS

2004 ◽  
Vol 13 (3) ◽  
pp. 46
Author(s):  
Martine Duval ◽  
Sara Bédard-Goulet ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Endothelial Cells ◽  
Down Regulation ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals The Ubiquitin−Proteasome Pathway Is Important for Dengue Virus Infection in Primary Human Endothelial Cells

2010 ◽  
Vol 9 (10) ◽  
pp. 4960-4971 ◽  
Author(s):  
Rattiyaporn Kanlaya ◽  
Sa-nga Pattanakitsakul ◽  
Supachok Sinchaikul ◽  
Shui-Tein Chen ◽  
Visith Thongboonkerd
Keyword(s):  
Endothelial Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
Human Endothelial Cells ◽  
Dengue Virus Infection ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals The RING Domain of cIAP1 Mediates the Degradation of RING-bearing Inhibitor of Apoptosis Proteins by Distinct Pathways

2008 ◽  
Vol 19 (7) ◽  
pp. 2729-2740 ◽  
Author(s):  
Herman H. Cheung ◽  
Stéphanie Plenchette ◽  
Chris J. Kern ◽  
Douglas J. Mahoney ◽  
Robert G. Korneluk
Keyword(s):  
Fas Ligand ◽  
Ring Domain ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Down Regulation ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Apoptosis Proteins

The Inhibitor of Apoptosis proteins (IAPs) are key repressors of apoptosis. Several IAP proteins contain a RING domain that functions as an E3 ubiquitin ligase involved in the ubiquitin-proteasome pathway. Here we investigated the interplay of ubiquitin-proteasome pathway and RING-mediated IAP turnover. We found that the CARD-RING domain of cIAP1 (cIAP1-CR) is capable of down-regulating protein levels of RING-bearing IAPs such as cIAP1, cIAP2, XIAP, and Livin, while sparing NAIP and Survivin, which do not possess a RING domain. To determine whether polyubiquitination was required, we tested the ability of cIAP1-CR to degrade IAPs under conditions that impair ubiquitination modifications. Remarkably, although the ablation of E1 ubiquitin-activating enzyme prevented cIAP1-CR–mediated down-regulation of cIAP1 and cIAP2, there was no impact on degradation of XIAP and Livin. XIAP mutants that were not ubiquitinated in vivo were readily down-regulated by cIAP1-CR. Moreover, XIAP degradation in response to cisplatin and doxorubicin was largely prevented in cIAP1-silenced cells, despite cIAP2 up-regulation. The knockdown of cIAP1 and cIAP2 partially blunted Fas ligand-mediated down-regulation of XIAP and protected cells from cell death. Together, these results show that the E3 ligase RING domain of cIAP1 targets RING-bearing IAPs for proteasomal degradation by ubiquitin-dependent and -independent pathways.

scholarly journals Sequential posttranslational modifications regulate PKC degradation

2016 ◽  
Vol 27 (2) ◽  
pp. 410-420 ◽  
Author(s):  
Yan Wang ◽  
Yangbo Wang ◽  
Huijun Zhang ◽  
Yingwei Gao ◽  
Chao Huang ◽  
...  
Keyword(s):  
Cross Talk ◽  
Posttranslational Modifications ◽  
Protein Function ◽  
Regulatory Mechanism ◽  
Down Regulation ◽  
Ubiquitin Proteasome Pathway ◽  
Different Types ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Cross-talk among different types of posttranslational modifications (PTMs) has emerged as an important regulatory mechanism for protein function. Here we elucidate a mechanism that controls PKCα stability via a sequential cascade of PTMs. We demonstrate that PKCα dephosphorylation decreases its sumoylation, which in turn promotes its ubiquitination and ultimately enhances its degradation via the ubiquitin-proteasome pathway. These findings provide a molecular explanation for the activation-induced down-regulation of PKC proteins.

Abstract 486: Down-regulation of type 1 cGMP-dependent Protein Kinase by the ubiquitin/proteasome pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
NUPUR DEY ◽  
Jennifer L Busch ◽  
Sharron H Francis ◽  
Jackie D Corbin ◽  
Thomas M Lincoln
Keyword(s):  
Protein Kinase ◽  
26S Proteasome ◽  
Down Regulation ◽  
Dependent Protein Kinase ◽  
Ubiquitin Proteasome Pathway ◽  
Cgmp Dependent Protein Kinase ◽  
Ubiquitin Proteasome ◽  
Dependent Protein ◽  
Proteasome Pathway

Type 1 cGMP-dependent protein kinase (PKG-I) is a widely expressed serine/threonine protein kinase, and is a major mediator of nitric oxide (NO) signaling in vascular smooth muscle cells (VSMC). PKG-I level is highly variable in VSMC and several studies have shown that atherogenic inflammatory cytokines lower the steady-statel levels of PKG-I. The mechanism of action of down-regulation is not well defined, but induction of type II NO synthase (iNOS) and subsequent persistent elevation of cGMP appear to contribute to PKG-I down regulation. In the present study, we examined the role of the ubiquitin/proteasome pathway in PKG-Iα down-regulation in response to elevated cGMP. Incubation of cultured VSMC with 8-Br-cGMP for 6–12 hr lowered PKG-I expression as assessed by western blotting. To further examine the mechanism, Cos7 cells, which do not express PKG-I mRNA or protein, were transfected with PKG-Iα/pcDNA vector and incubated with 8-Br-cGMP. 8-Br-cGMP suppressed PKG-Iα protein level in Cos7 cells (half-maximal concentration = 250 μM). Pretreatment of these cells with the proteasome inhibitor, MG132, followed by 8-Br-cGMP treatment prevented the decline suggesting the involvement of the ubiquitin/26S proteasome pathway. Immunoprecipitation of PKG-I followed by immunoblotting with anti-ubiquitin revealed multiple ubiquitinated PKG bands in the 8-Br-cGMP treated samples but not in untreated samples. Ubiquitination and down-regulation were also inhibited by the specific PKG-I catalytic inhibitor DT-2, suggesting the possible involvement of PKG autophosphorylation in the 8-Br-cGMP induced down-regulation. Mutation of the PKG-Iα autophosphorylation sites to alanines was performed to identify the phosphorylated site responsible for cGMP-dependent ubiquitination. In contrast to wild type PKG-Iα, PKG-Iα S64A, but not the S50A mutant, was not down-regulated by 8-Br-cGMP suggesting that autophosphorylation of serine-64 is required for the ubiquitination and down-regulation of PKG-I. Autophosphorylation and cGMP-mediated down-regulation of PKG-I may be an important mechanism to control excess cGMP signaling in VSMC.

Uraemic serum induces dysfunction of vascular endothelial cells: role of ubiquitin-proteasome pathway

2011 ◽  
Vol 96 (8) ◽  
pp. 801-815 ◽  
Author(s):  
Bing Feng ◽  
Yao-Quan Zhang ◽  
Jiao Mu ◽  
Fa-Huan Yuan ◽  
Zi-Lin Ye ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals Down-regulation of types I, II and III inositol 1,4,5-trisphosphate receptors is mediated by the ubiquitin/proteasome pathway

1999 ◽  
Vol 339 (2) ◽  
pp. 453 ◽  
Author(s):  
Jon OBERDORF ◽  
Jack M. WEBSTER ◽  
Chang Cheng ZHU ◽  
Su Ge LUO ◽  
Richard J.H. WOJCIKIEWICZ
Keyword(s):  
Down Regulation ◽  
Ubiquitin Proteasome Pathway ◽  
Inositol 1,4,5 Trisphosphate ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway
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