The COP9 signalosome controls ubiquitinylation of ABCA1

Azuma, Yuya; Takada, Mie; Maeda, Minami; Kioka, Noriyuki; Ueda, Kazumitsu

doi:10.1016/j.bbrc.2009.02.161

Cited by 29 publications

(18 citation statements)

References 28 publications

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“…It is already known that ABCA1 and ABCG1 can be degraded by proteasomal mechanisms (13,23,41,42), and this was confirmed in the present study, where degradation of both ABCA1 and ABCG1 was completely inhibited by proteasomal inhibitors, whereas lysosomal inhibitors were ineffective. This indicates that this process occurs in the endoplasmic reticulum and involves retrotranslocation.…”

Section: Discussionsupporting

confidence: 78%

“…Cholesterol loading did not affect overall protein ubiquitination in our system, suggesting that it may involve a relatively specific cholesterolsensitive E3 ligase or deubiqitinating enzyme. Recently, it was suggested that ABCA1 ubiquitination and proteolysis are controlled by the COP9 signalosome, and it would be interesting to determine whether this entity is cholesterol-sensitive (42). Several E3 ligases are known to exert cholesterol-dependent effects on the turnover of other membrane proteins (38,39,(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

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Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1

Hsieh

Kim

Gelissen

et al. 2014

Journal of Biological Chemistry

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Background: Cholesterol transporters ABCA1 and ABCG1 export excess cellular cholesterol and protect against atherosclerosis. Results: Cholesterol loading decreases cellular degradation of ABCA1 and ABCG1 and also their ubiquitination. Conclusion: Cholesterol-dependent suppression of ABCA1 and ABCG1 ubiquitination decreases their proteasomal degradation. Significance: This mechanism enhances the capacity of cholesterol-loaded cells to export their excess cholesterol.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1

Hsieh

Kim

Gelissen

et al. 2014

Journal of Biological Chemistry

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“…33 A recent report indicated that the COP9 signalosome complex regulates the ubiquitination status of ABCA1. 34 However, it remains unknown whether this complex has the ability to ubiquitinate ABCA1. Further studies are needed to explore in detail the function of the COP9 signalosome complex and to identify and characterize the E3s that localize close to the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Cellular Cholesterol Accumulation Facilitates Ubiquitination and Lysosomal Degradation of Cell Surface–Resident ABCA1

Mizuno

Hayashi

Kusuhara

2015

ATVB

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Objective-By excreting cellular cholesterol to apolipoprotein A-I, ATP-binding cassette transporter A1 (ABCA1) mediates the biogenesis of high-density lipoprotein in hepatocytes and prevents foam cell formation from macrophages. We recently showed that cell surface-resident ABCA1 (csABCA1) undergoes ubiquitination and later lysosomal degradation through the endosomal sorting complex required for transport system. Herein, we investigated the relevance of this degradation pathway to the turnover of csABCA1 in hypercholesterolemia. Approach and Results-Immunoprecipitation and cell surface-biotinylation studies with HepG2 cells and mouse peritoneal macrophages showed that the ubiquitination level and degradation of csABCA1 were facilitated by treatment with a liver X receptor (LXR) agonist and acetylated low-density lipoprotein. The effects of an LXR agonist and acetylated lowdensity lipoprotein on the degradation of csABCA1 were repressed completely by treatment with bafilomycin, an inhibitor of lysosomal degradation, and by depletion of tumor susceptibility gene 101, a major component of endosomal sorting complex required for transport-I. RNAi analysis indicated that LXRβ inhibited the accelerated lysosomal degradation of csABCA1 by the LXR agonist, regardless of its transcriptional activity. Cell surface coimmunoprecipitation with COS1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that LXRβ interacted with csABCA1 and inhibited the ubiquitination of csABCA1. Immunoprecipitates with anti-ABCA1 antibodies from the liver plasma membranes showed less LXRβ and a higher ubiquitination level of ABCA1 in high-fat diet-fed mice than in normal chow-fed mice. (csABCA1) is considered to be important to understanding the regulation of ABCA1 function. A key molecule for the degradation of csABCA1 is the protease calpain, which can cleave ABCA1 in the intracellular compartment or at the cell surface. Conclusions-Under15,16 However, calpain seems not to be involved in the accelerated degradation of ABCA1 induced by loading with free cholesterol and unsaturated fatty acids. 10,11 We recently found another degradation mechanism of csABCA1 that is independent of the calpain protease-involving machinery. Through this mechanism, ubiquitination, a regulated posttranslational modification that conjugates ubiquitin to lysine residues of targeted proteins, acts as a signal for the degradation of csABCA1 by the direction of ubiquitinated csABCA1 to lysosomal degradation. 17This degradation process involves the endosomal sorting complex required for transport (ESCRT) system, a set of proteins comprising ESCRT-0, -I, -II, and -III, which recognizes ubiquitinated cargo in the early endosome and mediates its recruitment to and incorporation into multivesicular bodies, leading to lysosomal degradation. [18][19][20] To explore the possibility of restoring the turnover of csABCA1 and inhibiting progression of atherosclerosis in hypercholesterolemia, in the current study, we focused on the ubiquitination-mediated lysosomal de...

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“…NTCP, BSEP, BCRP, and ABCA1 also undergo ubiquitination and proteasomal degradation Nakagawa et al, 2008;Azuma et al, 2009;Hayashi and Sugiyama, 2009;Wakabayashi-Nakao et al, 2009). Inhibition of the proteasome alters the subcellular localization of rat Ntcp from the plasma membrane of HepG2 cells to intracellular compartments .…”

Section: Ubiquitination and Sumoylationmentioning

confidence: 99%