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Revealing the human mucinome

Author

Listed:
  • Stacy A. Malaker

    (Stanford University
    Yale University)

  • Nicholas M. Riley

    (Stanford University)

  • D. Judy Shon

    (Stanford University)

  • Kayvon Pedram

    (Stanford University)

  • Venkatesh Krishnan

    (Stanford University)

  • Oliver Dorigo

    (Stanford University)

  • Carolyn R. Bertozzi

    (Stanford University
    Howard Hughes Medical Institute)

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.

Suggested Citation

  • Stacy A. Malaker & Nicholas M. Riley & D. Judy Shon & Kayvon Pedram & Venkatesh Krishnan & Oliver Dorigo & Carolyn R. Bertozzi, 2022. "Revealing the human mucinome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31062-4
    DOI: 10.1038/s41467-022-31062-4
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    References listed on IDEAS

    as
    1. Nicholas M. Riley & Alexander S. Hebert & Michael S. Westphall & Joshua J. Coon, 2019. "Capturing site-specific heterogeneity with large-scale N-glycoproteome analysis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Matthew J. Paszek & Christopher C. DuFort & Olivier Rossier & Russell Bainer & Janna K. Mouw & Kamil Godula & Jason E. Hudak & Jonathon N. Lakins & Amanda C. Wijekoon & Luke Cassereau & Matthew G. Rub, 2014. "The cancer glycocalyx mechanically primes integrin-mediated growth and survival," Nature, Nature, vol. 511(7509), pages 319-325, July.
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    Cited by:

    1. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Mathias I. Nielsen & Noortje Haan & Weston Kightlinger & Zilu Ye & Sally Dabelsteen & Minyan Li & Michael C. Jewett & Ieva Bagdonaite & Sergey Y. Vakhrushev & Hans H. Wandall, 2022. "Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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