Mucin 1 signal peptide (MUC1-SP) (MUC1-SP)

Mucin 1 (MUC1) is a type I transmembrane glycoprotein that is overexpressed and loses its apical polarity in various epithelial cancers, including breast, pancreatic, and lung carcinomas [1]. The MUC1 signal peptide (MUC1-SP) consists of the first 32 amino acids of the protein and is responsible for directing the nascent polypeptide to the endoplasmic reticulum for further processing [1]. While signal peptides are typically cleaved and degraded by the cell, research has demonstrated that the MUC1-SP is uniquely processed and presented as an epitope on the cell surface by MHC class I molecules, specifically HLA-A*02:01 [2]. This presentation allows the MUC1-SP to serve as a tumor-associated antigen (TAA) that can be recognized by cytotoxic T lymphocytes (CTLs) [3]. Consequently, the MUC1-SP is a target for immunotherapy, including peptide-based vaccines and T-cell receptor (TCR) engineered therapies, offering a distinct advantage over targeting the heavily glycosylated tandem repeat regions which can interfere with immune recognition [2, 4]. Sources: [1] UniProt Consortium. UniProtKB - P15941 (MUC1_HUMAN). [2] Feuerer, M., et al. (2001). Therapy of human tumors in NOD/SCID mice with patient-derived reactivity against a MUC1-signal peptide. Journal of Clinical Investigation. [3] Schwartz, K., et al. (2003). The MUC1 signal peptide is a naturally processed and HLA-A*0201-restricted tumor-associated antigen. Journal of Immunology. [4] Smialek, J., et al. (2021). MUC1 as a Target for Cancer Immunotherapy. Frontiers in Oncology.

Other names

MUC1 leader sequenceMUC-1 signal peptideCD227 signal peptideEMA signal peptidePolymorphic epithelial mucin signal peptide

Induction of a cytotoxic T-lymphocyte (CTL) response against tumor cells that present the MUC1 signal peptide fragment on MHC Class I molecules, specifically HLA-A*02:01 [2, 3].