PPARδ is a regulator of autophagy by its phosphorylation

Gou, Qian; Jiang, Yidan; Zhang, Runyun; Xü, Ying; Xu, Huihui; Zhang, Wenbo; Shi, Juanjuan; Hou, Yongzhong

doi:10.1038/s41388-020-1329-x

Cited by 21 publications

(16 citation statements)

References 58 publications

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“…Autophagy induces degradation of cytoplasmic materials and organelles in lysosomes, which plays an important role in maintaining cellular homeostasis 25 , 26 . In addition to the proteasome-dependent degradation discussed above, PD-L1 undergoes autophagic degradation by HIP1R and PKCα/GSK3β/MITF pathways 15 , 16 .…”

Section: The Pathways Of Pd-l1 Degradation By Autophagymentioning

confidence: 99%

PD-L1 degradation pathway and immunotherapy for cancer

et al. 2020

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Programmed death ligand 1 (PD-L1, CD274) is an essential immune checkpoint protein that binds to programmed death 1 (PD-1) on T-lymphocytes. T cell plays a critical role in killing cancer cells while the cancer cell exhibits immune escape by the expression of PD-L1. The binding of PD-L1 to PD-1 inhibits T cell proliferation and activity, leading to tumor immunosuppression. Increasing evidence shows that PD-L1 protein undergoes degradation in proteasomes or lysosomes by multiple pathways, leading to enhanced immunotherapy for cancer. Although some specific drugs induce PD-L1 degradation and increase antitumor activity, the combination of these drugs with PD-L1/PD-1 blockade significantly enhances cancer immunotherapy. In this review, we have discussed the interaction of PD-L1 degradation with cancer immunotherapy.

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Section: The Pathways Of Pd-l1 Degradation By Autophagymentioning

confidence: 99%

PD-L1 degradation pathway and immunotherapy for cancer

et al. 2020

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“…HSP90, Glut1, SLC1A5, EGFR, p‐EGFR (phsopho‐Tyr1092) antibodies were purchased from Sangon Botech. p‐PPARδ‐Y108 antibody was described previously 25 . Secondary antibodies were obtained from Jackson Immunoresearch.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, multiple EGFR inhibitors treatment effectively alleviates colorectal cancer progression 23,24 . Activated EGFR induces PPARδ‐Y108 phosphorylation leading to autophagy inhibition, 25 while it is still unclear the effect of PPARδ‐Y108 phosphorylation on cancer cell metabolism. Here we found that EGFR‐mediated PPARδ‐Y108 phosphorylation led to recruitment of HSP90 to PPARδ, subsequently, increased PPARδ protein stability and promoted cancer cell metabolism.…”

Section: Introductionmentioning

confidence: 99%

EGFR/PPARδ/HSP90 pathway mediates cancer cell metabolism and chemoresistance

Gou

Zhang

Xü

et al. 2020

J of Cellular Biochemistry

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Epidermal growth factor receptor (EGFR) induces peroxisome‐proliferator‐activated receptor‐δ (PPARδ)‐Y108 phosphorylation, while it is unclear the effect of phosphorylation of PPARδ on cancer cell metabolism. Here we found that EGF treatment increased its protein stability by inhibiting its lysosomal dependent degradation, which was reduced by gefitinib (EGFR inhibitor) treatment. PPARδ‐Y108 phosphorylation in response to EGF recruited HSP90 (heat shock protein 90) to PPARδ resulting in increased PPARδ stability. In addition, PPARδ‐Y108 phosphorylation promoted cancer cell metabolism, proliferation, and chemoresistance. Therefore, this study revealed a novel molecular mechanism of EGFR/HSP90/PPARδ pathway‐mediated cancer cell metabolism, proliferation, and chemoresistance, which provides a strategy for cancer treatment.

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“…The transcriptional activity of PPARδ is modulated by several factors, which are not well characterized but include post-translational modifications such as phosphorylation. Epidermal growth factor receptor (EGFR) has been recently shown to induce PPARδ phosphorylation at Y108 in response to epidermal growth factor (EGF) [13]. Although PPARδ contains several putative phosphorylation sites (Y108, T252, T253, T256), (https: //www.phosphosite.org/proteinAction.action?id=24004&showAllSites=true (accessed on 9 May 2021)) [14], little is known about phosphoregulation of PPARδ, in contrast to PPARα and PPARγ.…”

Section: Ppardelta: the Least Studied Ppar Isoformmentioning

confidence: 99%

PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming

Blunder

Pavel

Minzaghi

et al. 2021

IJMS

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Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed.

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PPARδ is a regulator of autophagy by its phosphorylation

Cited by 21 publications

References 58 publications

PD-L1 degradation pathway and immunotherapy for cancer

PD-L1 degradation pathway and immunotherapy for cancer

EGFR/PPARδ/HSP90 pathway mediates cancer cell metabolism and chemoresistance

PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming

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