Mucin-interacting proteins: from function to therapeutics

Abstract

Mucins are high molecular weight glycoproteins that are involved in regulating diverse cellular activities both in normal and pathological conditions. Mucin activity and localization is mediated by several molecular mechanisms, including discrete interactions with other proteins. An understanding of the biochemistry behind the known interactions between mucins and other proteins, coupled with an appreciation of their pathophysiological significance, can lend insight into the development of novel therapeutic agents. Indeed, a recent study demonstrated that a cell permeable inhibitor, PMIP, which disrupts the MUC1-EGFR interaction, is effective in killing breast cancer cells in vitro and in tumor models. KeywordsMucin; glycoproteins; interacting proteins; therapeutic Mucins and their interactions with other proteinsMucins are high molecular weight glycoproteins which can confer normal physiological protection and lubrication to epithelial surfaces [1,2]. Based on their sub-cellular localization, mucins are grouped into two different categories, secreted and membranebound. The secreted type mucins (MUC2, MUC5AC, MUC5B, MUC6-8 and MUC19) lack a transmembrane domain, and are secreted into the extra-cellular space. By contrast, the membrane-bound mucins (MUC1, MUC3, MUC4, MUC12-17 and MUC20) are type I membrane-anchored proteins with one membrane spanning domain, an NH2-terminal extracellular region, and a COOH-terminal intracellular cytoplasmic tail. Membrane-bound mucins can be released from the plasma membrane due to cleavage; alternative splicing can also produce secreted variants [1,3]. Although all mucins are encoded by different genes, their primary protein structures share some characteristic similarities (Box 1). In addition to these similarities, however, the primary structures of different mucins also harbor many unique functional domains and motifs which are specific to an individual or group of mucins [1,2]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptTrends Biochem Sci. Author manuscript; available in PMC 2011 April 1. Burgeoning evidence indicates that due to their specialized structures, different mucins interact with distinct protein partners. These interactions provide specificity to mucinmediated molecular and cellular events. Importantly, in various cancers, the deregulated expression and structural modifications of mucins drive protein-protein interactions which can impact cancer progression. Given that major membrane-bound mucins regulate different cancer promoting signaling events [4], and that some mucins ar...

Isolation, Biochemical Characterization and Anti-adhesion Property of Mucin from the Blue Blubber Jellyfish (<i>Catostylus mosaicus</i>)

“…Jellyfish are known to secret mucus to help clean their surface and to discourage attacks by predators (Hanaoka et al, 2001). In addition and like their mammalian counterparts, mucins secreted by jellyfish together with their interacting proteins may function to mediate various cellular activities to enhance physical protection, enhance tissue integrity and enhance non-immune host defence (Senapati et al, 2010). These activities allow the jellyfish to survive in their aqueous habitat.…”

Membranous Expression of Ectodomain Isoforms of the Epidermal Growth Factor Receptor Predicts Outcome after Chemoradiotherapy of Lymph Node–Negative Cervical Cancer

“…The ICD was beneficial for this interaction, but not essential, and TK activation was not involved. EGFR interaction through the ECD with other membranous oncoproteins such as the mucin MUC1 has also been reported (26). It is possible that ectodomain EGFR isoforms could serve as a stabilizer and/or activator of these proteins in a similar way as the fulllength receptor and thereby promote tumorigenic signaling.…”

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

“…The viscoelastic properties of mucus, slimes, and other viscous biofluids are determined in large part by the formation of extended and entangled structures by mucins such as the SCPP mucin 7 (Supplementary Table S4, http:// dx.doi.org/10.3168/jds.2013-6831; Schenkels et al, 1995;Thornton et al, 2008;Senapati et al, 2010). Likewise, P,Q-rich proteins readily form gels; for example, the seed storage prolamins wheat gliadin and barley hordein (Shewry and Halford, 2002) or the plant cell wall extensins (Newman and Cooper, 2011).…”