Threonine aspartase 1 (TASP1)

Threonine aspartase 1 (TASP1) is a highly conserved threonine endopeptidase enzyme required for the proteolytic cleavage of nuclear proteins at specific aspartate-containing motifs. It is expressed as a proenzyme that undergoes autoproteolysis to form active α/β heterodimers, functioning as an α₂β₂ heterotetramer. TASP1’s primary biological substrates are regulatory proteins such as mixed-lineage leukemia proteins (MLL1/KMT2A, MLL2/KMT2B) and general transcription factors (TFIIA, ALF), which require site-specific cleavage for functional maturation. TASP1 orchestrates critical genetic programs involved in cell cycle regulation, cell fate specification, and tissue development, especially through regulation of HOX gene expression and cell cycle genes. TASP1 is not a classical oncogene but is generally overexpressed in human cancers, where it supports tumor proliferation and survival by enabling non-oncogene addiction programs. Inherited loss-of-function mutations in TASP1 are linked to severe developmental syndromes affecting hematopoiesis, craniofacial morphology, and the skeleton. TASP1’s essential cellular roles make it a proposed, but therapeutically challenging, anticancer target.

Other names

TASP1C20orf13dJ585I14.2taspase 1SULEHSthreonine aspartase 1Threonine aspartase subunit alphaThreonine aspartase subunit betaFLJ20212

Site-specific inhibition of Taspase 1 proteolytic activity (leading to disrupted cleavage of substrates and block of downstream genetic programs that support cell proliferation and cancer cell survival)