Cells, Vol. 12, Pages 363: Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription

Cells, Vol. 12, Pages 363: Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription

Cells doi: 10.3390/cells12030363

Authors: Lisa Oelschläger Paul Stahl Farnusch Kaschani Roland H. Stauber Shirley K. Knauer Astrid Hensel

The human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1's biology is, however, still poorly understood, and so far its cellular function was not assigned to a superordinate biological pathway or a specific signaling cascade. Our data, gained by methods such as co-immunoprecipitation, LC-MS/MS and Topoisomerase II DNA cleavage assays, now functionally link Taspase1 and hormone-induced, Topoisomerase IIβ-mediated transient DNA double-strand breaks, leading to active transcription. The specific interaction with Topoisomerase IIα enhances the formation of DNA double-strand breaks that are a key prerequisite for stimulus-driven gene transcription. Moreover, Taspase1 alters the H3K4 epigenetic signature upon estrogen-stimulation by cleaving the chromatin-modifying enzyme MLL. As estrogen-driven transcription and MLL-derived epigenetic labelling are reduced upon Taspase1 siRNA-mediated knockdown, we finally characterize Taspase1 as a multifunctional co-activator of estrogen-stimulated transcription.