Article from the Stenmark group selected "JBC Paper of the week"
Thomas Slagsvold
A paper from the Stenmark group, entitled "Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain," with Thomas Slagsvold (photo) as first writer, has been selected as a Journal of Biological Chemistry Paper of the Week. The paper appeared in the May 20 issue of the journal. The Papers of the Week is a feature of JBC Online. Their Editorial Board members and Associate Editors are asked to select papers that rank in the top 1% of papers they will review in a year in significance and overall importance. About 50-100 papers are each year from the over 6600 that are published.
Ubiquitination serves as a key sorting signal in the lysosomal degradation of endocytosed receptors through the ability of ubiquitinated membrane proteins to be recognized and sorted by ubiquitin-binding proteins along the endocytic route. The ESCRT-II complex in yeast contains one such protein, Vps36, which harbors a ubiquitin-binding NZF domain and is required for vacuolar sorting of ubiquitinated membrane proteins. Surprisingly, the presumptive mammalian ortholog Eap45 lacks the ubiquitin-binding module of Vps36, and it is thus not clear whether mammalian ESCRT-II functions to bind ubiquitinated cargo. In this paper, we provide evidence that Eap45 contains a novel ubiquitin-binding domain, GLUE (GRAM-like ubiquitin-binding in Eap45), which binds ubiquitin with similar affinity and specificity as other ubiquitin-binding domains. The GLUE domain shares similarities in its primary and predicted secondary structures to phosphoinositide-binding GRAM and PH domains. Accordingly, we find that Eap45 binds to a subset of 3-phosphoinositides, suggesting that ubiquitin recognition could be coordinated with phosphoinositide binding. Furthermore, we show that Eap45 colocalizes with ubiquitinated proteins on late endosomes. These results are consistent with a role for Eap45 in endosomal sorting of ubiquitinated cargo.
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Fackler MJ, Pleas M, Li Y, Soni A, Xing D, Cope L, Ali S, Van Le Q, Van Nguyen C, Pham HT, Duong LM, Vanden Berg E, Wadee R, Michelow P, Chen WC, Joffe M, Fjeldbo CS, Lyng H, Sukumar S(2024) Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries Clin Epigenetics, 16(1), 56 DOI 10.1186/s13148-024-01669-z, PubMed 38643219
Grindedal EM, Zucknick M, Stormorken A, Rønne E, Tandstad NM, Isaacs WB, Axcrona K, Mæhle L(2024) Outcomes of 10 years of PSA screening for prostate cancer in Norwegian men with Lynch syndrome Prostate(in press) DOI 10.1002/pros.24711, PubMed 38629217
