Caveolin-1 Inhibits Expression of Antioxidant Enzymes through Direct Interaction with Nuclear Erythroid 2 p45-related Factor-2 (Nrf2)

Li, Wen; Liu, Hui; Zhou, Jie; Cao, Jiao; Zhou, Xiao; Choi, Augustine M.K.; Chen, Zhi Hua; Shen, Hua

doi:10.1074/jbc.m112.352336

Cited by 78 publications

(60 citation statements)

References 37 publications

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“…The typical Cav-1-protein interaction occurs through the scaffolding domain in Cav-1 and the CBM in target proteins, such as endothelial nitric oxide synthase (11), Tolllike receptor 4 (40), and activin receptor-like kinase 1 (37). We have recently observed that the autophagy protein LC3B and transcription factor nuclear erythroid 2 p45-related factor-2 (Nrf2), respectively, contain amino acid sequences very similar to CBM, and these similar structures mediate the interactions of Cav-1-LC3B (4) and Cav-1-Nrf2 (22). In the present study, we have also found that a typical CBM is presented in ATG12, which also mediates its interaction with Cav-1, as mutation of the CBM in ATG12 effectively disrupted their association.…”

Section: Discussionmentioning

confidence: 99%

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Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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AM, Shen H. Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 306: L1016 -L1025, 2014. First published April 11, 2014 doi:10.1152/ajplung.00268.2013.-Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse environments, although the regulation of this process remains incompletely understood. We have recently observed that caveolin-1 (Cav-1), a major constituent of lipid rafts on plasma membrane, can regulate autophagy in cigarette smoking-induced injury of lung epithelium, although the underlying molecular mechanisms remain incompletely understood. In the present study we found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an ubiquitin-like conjugation system crucial for autophagosome formation, in lung epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5. Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy but resulted in decreased interactions between Cav-1 and another molecule. Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1 binding motif on ATG12 disrupted their interaction and further augmented autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy protein associating with the ATG12-ATG5 conjugate during autophagosome formation. Altogether these studies clearly demonstrate that Cav-1 competitively interacts with the ATG12-ATG5 system to suppress the formation and function of the latter in lung epithelial cells, thereby providing new insights into the molecular mechanisms by which Cav-1 regulates autophagy and suggesting the important function of Cav-1 in certain lung diseases via regulation of autophagy homeostasis.caveolin-1; ATG12-ATG5; ATG16L; autophagy; lung diseases AUTOPHAGY IS A DYNAMIC PROCESS responsible for the turnover of cellular organelles and long-lived proteins. During this process, cytosolic proteins and organelles (e.g., mitochondria and endoplasmic reticulum) are engulfed into double-membranebound vesicles, autophagosomes. The outer membrane of the autophagosome subsequently fuses with lysosomes to form autolysosomes in which the engulfed components are degraded by lysosomal hydrolases, regenerating metabolic precursors that are recycled for macromolecular synthesis and ATP generation (20, 42). Autophagy is induced above basal levels in response to diverse stimuli including nutrient starvation, genotoxic agents, cytokines, and oxidative stress. This process provides an essential function in the maintenance of cellular homeostasis and adaptation to adverse environments (16,29,35).More than 30 autophagy-related genes and gene products critical in the regulation of autophagy, designated "ATG," have been identified heretofore in yeast and hi...

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Section: Discussionmentioning

confidence: 99%

“…3B). In fact, we have recently observed that, in Beas-2B cells, Cav-1 distributed majorly in cytosol as well as in nucleus (22).…”

Section: Atg12-atg5 Interacts With Cav-1 In Cytosolmentioning

confidence: 93%

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In ovarian carcinoma cell lines, Cav-1 regulates cell cycle regulatory gene expression through direct DNA binding (37). Cav-1 also affects transcription in lung epithelial Beas-2B cells by directly binding the transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2) (38). Our previous work (17) revealed an interaction between Cav-1 and GR in NPSCs.…”

Section: Resultsmentioning

confidence: 96%

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

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While glucocorticoids (GCs) are used clinically to treat many conditions, their neonatal and prenatal usage is increasingly controversial due to reports of delayed adverse outcomes, especially their effects on brain development. Such alterations may reflect the impact of GCs on neural progenitor/stem cell (NPSC) function. We previously demonstrated that the lipid raft protein caveolin-1 (Cav-1) was required for rapid GC signaling in embryonic mouse NPSCs operating through plasma membranebound glucocorticoid receptors (GRs). We show here that genomic GR signaling in NPSCs requires Cav-1. Loss of Cav-1 impacts the transcriptional response of many GR target genes (e.g., the serum-and glucocorticoid-regulated kinase 1 gene) that are likely to mediate the antiproliferative effects of GCs. Microarray analysis of wild-type C57 or Cav-1-deficient NPSCs identified approximately 100 genes that are differentially regulated by GC treatment. These changes in hormone responsiveness in Cav-1 knockout NPSCs are associated with the loss of GC-regulated phosphorylation of GR at serine 211 but not at serine 226. Chromatin recruitment of total GR to regulatory regions of target genes such as Fkbp-5, RhoJ, and Sgk-1, as well as p211-GR recruitment to Sgk-1, are compromised in Cav-1 knockout NPSCs. Cav-1 is therefore a multifunctional regulator of GR in NPSCs influencing both rapid and genomic action of the receptor to impact cell proliferation.

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“…We employed an RNAi-based approach utilising previously published siRNA which we have previously employed to silence expression of aadaptin, a critical component of the clathrin-mediated endocytosis machinery, in HeLa cells (Rappoport and Simon, 2008;Rappoport and Simon, 2009), or caveolin1 (Li et al, 2012), which is required for caveolae formation (Rothberg et al, 1992). Control experiments revealed that a-adaptin siRNA treatment significantly inhibited transferrin endocytosis (supplementary material Fig.…”

Section: Fgfr Is Internalized Through Clathrin-mediated Endocytosismentioning

confidence: 99%

Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8

Auciello

Cunningham

Tatar

et al. 2013

Journal of Cell Science

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SummaryFibroblast growth factor receptors (FGFRs) mediate a wide spectrum of cellular responses that are crucial for development and wound healing. However, aberrant FGFR activity leads to cancer. Activated growth factor receptors undergo stimulated endocytosis, but can continue to signal along the endocytic pathway. Endocytic trafficking controls the duration and intensity of signalling, and growth factor receptor signalling can lead to modifications of trafficking pathways. We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. Activated FGFR enters the cell following recruitment to pre-formed clathrin-coated pits (CCPs). However, FGFR activation stimulates clathrin-mediated endocytosis; FGF treatment increases the number of CCPs, including those undergoing endocytosis, and this effect is mediated by Src and its phosphorylation target Eps8. Eps8 interacts with the clathrin-mediated endocytosis machinery and depletion of Eps8 inhibits FGFR trafficking and immediate Erk signalling. Once internalized, FGFR passes through peripheral early endosomes en route to recycling and degredative compartments, through an Src-and Eps8-dependent mechanism. Thus Eps8 functions as a key coordinator in the interplay between FGFR signalling and trafficking. This work provides the first detailed mechanistic analysis of growth factor receptor clustering at the cell surface through signal transduction and endocytic trafficking. As we have characterised the Src target Eps8 as a key regulator of FGFR signalling and trafficking, and identified the early endocytic system as the site of Eps8-mediated effects, this work provides novel mechanistic insight into the reciprocal regulation of growth factor receptor signalling and trafficking.

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Caveolin-1 Inhibits Expression of Antioxidant Enzymes through Direct Interaction with Nuclear Erythroid 2 p45-related Factor-2 (Nrf2)

Cited by 78 publications

References 37 publications

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8

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