Signal-transducing adaptor protein 1 (STAP1)

Signal-transducing adaptor protein 1 (STAP1) is an intracellular adaptor protein encoded by the STAP1 gene in humans. It is primarily characterized by a pleckstrin homology (PH) domain and a Src homology 2 (SH2)-like domain, which enable its role as a docking protein in multiple intracellular signaling pathways, including those downstream of Tec tyrosine kinase in B cell antigen receptor signaling and STAT5-mediated pathways in hematopoietic and immune cells. STAP1 participates in positive feedback amplification of Tec activity and is involved in the maintenance of leukemia stem cells (LSCs), modulating their survival and apoptotic resistance mainly via STAT5 signaling. It also regulates activation and survival of invariant natural killer T cells and may be implicated in the maintenance of cholesterol homeostasis and the pathogenesis of diseases such as familial hypercholesterolemia, chronic myeloid leukemia, and autoimmune hepatitis. Modulation of STAP1 function has shown synergistic effects with known kinase inhibitors in preclinical cancer models, suggesting its potential as a therapeutic target, though safety and specificity challenges remain due to its roles in normal immune and hematopoietic processes.

Other names

BRDG1BCR downstream-signaling protein 1docking protein BRDG1stem cell adaptor protein 1BCR downstream signaling 1

Inhibition of STAP1 enhances sensitivity of leukemia stem cells to tyrosine kinase inhibitors (e.g., imatinib) and JAK2 inhibitors (e.g., ruxolitinib) by promoting apoptosis via downregulation of anti-apoptotic genes through STAT5 signaling pathway