CYLD/HDAC6 signaling regulates the interplay between epithelial-mesenchymal transition and ciliary homeostasis during pulmonary fibrosis DOI Creative Commons
Hua Ni, Miao Chen, Dan Dong

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 9, 2024

The primary cilium behaves as a platform for sensing and integrating extracellular cues to control plethora of cellular activities. However, the functional interaction this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal critical role cylindromatosis (CYLD) in reciprocally linking EMT program ciliary homeostasis fibrosis. A close correlation between cilia is observed bleomycin-induced well TGF-β-induced model. Mechanistic study reveals that downregulation CYLD underlies crosstalk by inactivating histone deacetylase 6 (HDAC6) Moreover, manipulation an effective means modulate program. Collectively, these results identify pivotal CYLD/HDAC6 signaling regulating reciprocal interplay

Language: Английский

KIF11 UFMylation Maintains Photoreceptor Cilium Integrity and Retinal Homeostasis DOI
Jie Ran,

Guizhi Guo,

Sai Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(25)

Published: April 26, 2024

Abstract The photoreceptor cilium is vital for maintaining the structure and function of retina. However, molecular mechanisms underlying integrity retinal homeostasis are largely unknown. Herein, it shown that kinesin family member 11 (KIF11) localizes at transition zone (connecting cilium) plays a crucial role in orchestrating integrity. KIF11 depletion causes malformations both ciliary axoneme membranous discs, resulting degeneration accumulation drusen‐like deposits throughout Mechanistic studies show stability regulated by an interplay between its UFMylation ubiquitination; lysine 953 inhibits ubiquitination synoviolin 1 thereby prevents proteasomal degradation. 953‐to‐arginine mutant more stable than wild‐type also effective reversing defects induced depletion. These findings identify critical maintenance homeostasis.

Language: Английский

Citations

10
Targeted degradation of membrane and extracellular proteins with LYTACs DOI

Yuyang Li,

Yang Yang, Renshuai Zhang

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Language: Английский

Citations

9
UFMylation: An integral post-translational modification for the regulation of proteostasis and cellular functions DOI
Xiaohui Wang,

Xiaowei Lv,

Jingjing Ma

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 260, P. 108680 - 108680

Published: June 13, 2024

Language: Английский

Citations

4
Targeted degradation of VEGF with bispecific aptamer-based LYTACs ameliorates pathological retinal angiogenesis DOI Creative Commons
Ping Zhou, Sai Zhang,

Li Lin

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(13), P. 4983 - 5000

Published: Jan. 1, 2024

Neovascular ocular diseases (NODs) represent the leading cause of visual impairment globally. Despite significant advances in anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF), persistent challenges remain prevalent. As a proof-of-concept study, we herein demonstrate effectiveness targeted degradation VEGF with bispecific aptamer-based lysosome-targeting chimeras (referred to as VED-LYTACs).

Language: Английский

Citations

4
Multifaceted roles of UFMylation in health and disease DOI Creative Commons
R. Wang, Li Lin, Jun Zhou

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

0
KIF11 Inhibition Induces Retinopathy Progression by Affecting Photoreceptor Cell Ciliogenesis and Cell Cycle Regulation in Development DOI Open Access

Yue Xu,

Jie Chen,

Xin‐Yao Wang

et al.

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Microcephaly with or without chorioretinopathy, lymphedema, impaired intellectual development (MCLMR; OMIM 152950) is a rare autosomal dominant disorder, which primarily characterized by defects in the central nervous system and retinal developmental anomalies. Kinesin‐5 KIF11 has been discovered as major causative gene for MCLMR. It well established that essential microtubule organization, centrosome separation, spindle assembly during mitosis. However, cellular molecular mechanisms physiopathology of MCLMR remain largely unknown. In this study, KIF11‐inhibition mouse models are generated, reveal chemical inhibition results development, formation rosettes, photoreceptor ciliary alterations, vision loss. Furthermore, it demonstrated formation, maintenance primary cilia cells, further contributes to organization cells retina. Using developing embryos model, revealed induces monopolar mitotic arrest, tetraploidy apoptotic cell death. These findings uncover underlying loss‐of‐function retinopathy support functions development.

Language: Английский

Citations

0
UFMylation Modulates OFIP Stability and Centrosomal Localization DOI Creative Commons
Mulin Yang,

Zhiyang Zhao,

Jie Di

et al.

Journal of Clinical Laboratory Analysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

OFIP, also known as KIAA0753, is a centrosomal and pericentriolar satellite protein implicated in ciliogenesis, centriolar duplication, microtubule stability. In humans, genetic mutations affecting OFIP have been the pathogenesis of Oral-Facial-Digital (OFD) Syndrome Joubert Syndrome. Ubiquitin-fold Modifier 1 (UFM1), most recently identified ubiquitin-like protein, covalently transferred to its substrates, process UFMylation. This modification has emerged key regulator various biological processes by altering their stability, activity, or localization. The interaction between UFL1 well UFMylation were assessed through immunoprecipitation immunoblotting analyses. mRNA levels examined using reverse transcription quantitative PCR (RT-qPCR). Immunofluorescence microscopy was employed examine localization distribution patterns OFIP. Our findings demonstrate that interacts with both vivo vitro. We found undergoes UFMylation, promotes Mechanistic studies inhibits stability maintains proper However, efficacy these regulatory mechanisms varies significantly different cell types, being notably pronounced HeLa cells but markedly reduced RPE1 cells. novel substrate for UFL1-mediated essential effects are not observed cells, highlighting type-specific heterogeneity role

Language: Английский

Citations

0
CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments DOI Creative Commons
Song Yang, Yu Fan, Mulin Yang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(45)

Published: Oct. 7, 2024

Abstract Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for homeostasis. Dysregulation phagocytotic process associated with irreversible degenerative diseases. However, molecular mechanisms underlying phagocytic activity RPE cells remain elusive. In an effort to uncover proteins orchestrating function, cylindromatosis (CYLD) deubiquitinase identified as a critical regulator segment phagocytosis. CYLD‐deficient mice exhibit abnormal structure and function. Mechanistically, CYLD interacts enkurin domain containing protein 1 (ENKD1) deubiquitinates ENKD1 at lysine residues K141 K242. Deubiquitinated Ezrin, membrane‐cytoskeleton linker, stimulates microvillar localization which cells. These findings thus reveal crucial role CYLD‐ENKD1‐Ezrin axis in regulating homeostasis may have important implications prevention treatment

Language: Английский

Citations

2
Disruption of photoreceptor cilia is a critical event in the pathogenesis of retinal degeneration—Insights from N-methyl-N-nitrosourea-induced mouse model DOI Creative Commons

Guizhi Guo,

Runa Wang,

Yufei Zhang

et al.

Medicine Plus, Journal Year: 2024, Volume and Issue: 1(3), P. 100040 - 100040

Published: July 4, 2024

Language: Английский

Citations

1
CYLD/HDAC6 signaling regulates the interplay between epithelial-mesenchymal transition and ciliary homeostasis during pulmonary fibrosis DOI Creative Commons
Hua Ni, Miao Chen, Dan Dong

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 9, 2024

The primary cilium behaves as a platform for sensing and integrating extracellular cues to control plethora of cellular activities. However, the functional interaction this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal critical role cylindromatosis (CYLD) in reciprocally linking EMT program ciliary homeostasis fibrosis. A close correlation between cilia is observed bleomycin-induced well TGF-β-induced model. Mechanistic study reveals that downregulation CYLD underlies crosstalk by inactivating histone deacetylase 6 (HDAC6) Moreover, manipulation an effective means modulate program. Collectively, these results identify pivotal CYLD/HDAC6 signaling regulating reciprocal interplay

Language: Английский

Citations

1