Delta-like homologue 1 (DLK1)

Delta-like homologue 1 (DLK1), also known as Preadipocyte factor 1 (Pref-1), is a transmembrane glycoprotein that functions as a non-canonical ligand in the Notch signaling pathway (UniProt P80370). It is characterized by the presence of six epidermal growth factor-like repeats but lacks the Delta/Serrate/LAG-2 (DSL) domain typical of other Notch ligands, allowing it to act as an inhibitor of Notch signaling (PubMed: 24511468). Biologically, DLK1 is a critical regulator of cell fate, particularly in inhibiting the differentiation of preadipocytes into adipocytes and maintaining the undifferentiated state of stem cells (PubMed: 11013310). In clinical oncology, DLK1 is recognized as a tumor-associated antigen due to its significant overexpression in various cancers, such as hepatocellular carcinoma and small cell lung cancer, while its expression in healthy adult tissues is highly restricted (PubMed: 21814174). Consequently, DLK1-derived peptide antigens are being investigated as targets for immunotherapy, including peptide vaccines and TCR-engineered T-cell therapies, designed to elicit a specific cytotoxic T-lymphocyte response against malignant cells (PubMed: 30206144).

Other names

Preadipocyte factor 1Pref-1Fetal antigen 1FA1Delta-like protein 1pG2SeclZOG

Peptide antigens derived from the DLK1 protein are processed and presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of tumor cells. These peptide-MHC complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then trigger the release of perforins and granzymes to induce apoptosis in the target cancer cell (PubMed: 21814174, 30206144).