Alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1)

Alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1) is a cytoplasmic protein characterized by the presence of a UBX domain and functions primarily as a tether for the glucose transporter type 4 (GLUT4), controlling its sequestration in intracellular vesicles and regulating its movement to the plasma membrane in response to insulin in muscle and adipose tissues[5][4]. ASPSCR1 also antagonizes the AAA+ ATPase valosin-containing protein (VCP/p97), regulating its role in protein unfolding, autophagy, and the quality control of protein folding in the endoplasmic reticulum[1]. A notable role of ASPSCR1 is its involvement in cancer through a chromosomal translocation t(X;17)(p11;q25) generating the ASPSCR1-TFE3 fusion, which produces an oncogenic transcriptional regulator that drives proliferation, angiogenesis, and metabolic reprogramming in alveolar soft part sarcoma and certain renal cell carcinomas[3][5]. Treatments targeting downstream effectors regulated by the fusion, such as the cyclin D1/CDK4 axis and epigenetic co-activators (BRD4, CDK7), show preclinical therapeutic potential in models of ASPS[3]. ASPSCR1 thus represents both a crucial regulator of GLUT4 trafficking and a key oncogenic driver through its fusion with TFE3 in specific cancers.

Other names

Tether containing UBX domain for GLUT4ASPLRCC17TUGUBXD9UBXN9ASPCR1Renal papillary cell carcinoma protein 17UBX domain protein 9UBX domain-containing protein 9

Inhibition of cyclin D1/CDK4 axis, disrupting cell cycle progression in ASPS driven by ASPSCR1::TFE3 fusion[3] Inhibition of BRD4 and CDK7 disrupting transcriptional programs in ASPSCR1::TFE3-positive cells[3]