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Revealing the human mucinome.
Malaker, Stacy A; Riley, Nicholas M; Shon, D Judy; Pedram, Kayvon; Krishnan, Venkatesh; Dorigo, Oliver; Bertozzi, Carolyn R.
Affiliation
  • Malaker SA; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, 94305, CA, USA. stacy.malaker@yale.edu.
  • Riley NM; Department of Chemistry, Yale University, New Haven, 06511, CT, USA. stacy.malaker@yale.edu.
  • Shon DJ; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, 94305, CA, USA.
  • Pedram K; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, 94305, CA, USA.
  • Krishnan V; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, 94305, CA, USA.
  • Dorigo O; Stanford Women's Cancer Center, Division of Gynecologic Oncology, Stanford University, Stanford, 94305, CA, USA.
  • Bertozzi CR; Stanford Women's Cancer Center, Division of Gynecologic Oncology, Stanford University, Stanford, 94305, CA, USA.
Nat Commun ; 13(1): 3542, 2022 06 20.
Article in En | MEDLINE | ID: mdl-35725833
ABSTRACT
Mucin domains are densely O-glycosylated modular protein domains found in various extracellular and transmembrane proteins. Mucin-domain glycoproteins play important roles in many human diseases, such as cancer and cystic fibrosis, but the scope of the mucinome remains poorly defined. Recently, we characterized a bacterial O-glycoprotease, StcE, and demonstrated that an inactive point mutant retains binding selectivity for mucin-domain glycoproteins. In this work, we leverage inactive StcE to selectively enrich and identify mucin-domain glycoproteins from complex samples like cell lysate and crude ovarian cancer patient ascites fluid. Our enrichment strategy is further aided by an algorithm to assign confidence to mucin-domain glycoprotein identifications. This mucinomics platform facilitates detection of hundreds of glycopeptides from mucin domains and highly overlapping populations of mucin-domain glycoproteins from ovarian cancer patients. Ultimately, we demonstrate our mucinomics approach can reveal key molecular signatures of cancer from in vitro and ex vivo sources.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Mucins Limits: Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Mucins Limits: Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Type: Article Affiliation country: United States