UFMylation Modulates OFIP Stability and Centrosomal Localization

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

CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments

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