Novel roles for mucin 1 in the kidney

Abstract

Purpose of the review Recent studies in the kidney have revealed that the well-characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. Recent findings Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance. Our recent studies in mice show that mucin 1 is induced after ischemia, stabilizing HIF-1α and β-catenin levels, and transactivating the HIF-1 and β-catenin protective pathways. However, prolonged induction of either pathway in the injured kidney can proceed from apparent full recovery to chronic kidney disease. A very recent report indicates that aberrant activation of mucin1 signaling after ischemic injury in mice and humans is associated with development of chronic kidney disease and fibrosis. A frame-shift mutation in MUC1 was recently identified as the genetic lesion causing Medullary Cystic Kidney Disease type 1, now appropriately renamed MUC1 Kidney Disease (MKD). Summary Studies of mucin 1 in the kidney now reveal significant functions for the extracellular mucin-like domain and signaling through the cytoplasmic tail.

Differential Urinary Proteome Analysis for Predicting Prognosis in Type 2 Diabetes Patients with and without Renal Dysfunction

“…Cystatin A (CTSA), in the same protein family as cystatin C that can measure kidney function [ 44 , 45 , 46 ], has been found in our urinary biomarker discovery study. Muc1 is a multifaceted tumor protein, and its relationship with the kidney has recently been highlighted [ 47 ] and has been identified as a mutant that causes mendelian disorder medullary cystic kidney disease type 1 [ 48 ]. In a meta-analysis study of rat glomerular transcriptome profiling, it was confirmed that GM2A was highly expressed in various diabetic kidney disease rat [ 49 ].…”

MUC1 intracellular bioactivation mediates lung fibrosis

“…The MUC1-CT nuclear translocation is also mediated by a mechanism that is dependent on its oligomerisation, and thus involves interaction with importin β 11. Mucin dimerisation through the CQC motif (the first three aa of the MUC1-CT 72 aa region) yields a nuclear targeting signal based on the adjacent RRK motif, thus promoting MUC1-CT nuclear internalisation 33. In this regard, blocking the MUC1-CT CQC motif abrogates oligomerisation, and is therefore a target for pharmacological treatments to inhibit MUC1-CT nuclear localisation and transcriptional function.…”

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

“…The MUC1 membrane mucin is a high-molecular-mass glycoprotein encoded by the muc1 gene, also called CD227, which was first identified through a monoclonal antibody binding experiment (77). It is well-known that MUC1 promotes cell growth and survival (78). Evidence shows that the overexpression of MUC1 is related to cell adhesion inhibition and the increased metastatic potential of tumor cells, especially in breast cancer (79).…”