title: PHF23 (plant homeodomain finger protein 23) negatively regulates cell autophagy by promoting ubiquitination and degradation of E3 ligase LRSAM1.
abstract: Autophagy is a multistep process that involves the degradation and digestion of intracellular components by the lysosome. It has been proved that many core autophagy-related molecules participate in this event. However, new component proteins that regulate autophagy are still being discovered. At present, we report PHF23 (PHD finger protein 23) with a PHD-like zinc finger domain that can negatively regulate autophagy. Data from experiments indicated that the overexpression of PHF23 impaired autophagy, as characterized by decreased levels of LC3B-II and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, knockdown of PHF23 resulted in opposite effects. Molecular mechanism studies suggested that PHF23 interacts with LRSAM1, which is an E3 ligase key for ubiquitin-dependent autophagy against invading bacteria. PHF23 promotes the ubiquitination and proteasome degradation of LRSAM1. We also show that the PHD finger of PHF23 is a functional domain needed for the interaction with LRSAM1. Altogether, our results indicate that PHF23 is a negative regulator associated in autophagy via the LRSAM1 signaling pathway. The physical and functional connection between the PHF23 and LRSAM1 needs further investigation.
authors.affiliation: a Key Laboratory of Medical Immunology; Ministry of Health ; Peking University Health Science Center ; Beijing , China.
authors.forename: Zhenda
authors.initials: Z
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Liujing
authors.initials: L
authors.lastname: Qu
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lou
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Song
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C523053:PHF23 protein, human; D025801:Ubiquitin; C489657:LRSAM1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: AML, acute myeloid leukemia; ATG, autophagy-related; BafA1, bafilomycin A1; CALCOCO2, calcium binding and coiled-coil domain 2; CQ, chloroquine; EBSS, Earle's balanced salt solution; FBS, fetal bovine serum; GFP, green fluorescent protein; GST, glutathione S-transferase; IP, immunoprecipitation; LRSAM1; LRSAM1, leucine rich repeat and sterile α motif containing 1; MAP1LC3B/LC3B; PHD domain; PHD, plant homeodomain; PHF23; PHF23, PHD finger protein 23; PIK3C3, phosphatidylinositol 3-kinase, catalytic subunit type 3; SQSTM1, sequestosome 1; Three-MA, 3-methyladenine; autophagy; microtubule-associated protein 1 light chain 3 β; ubiquitination