title: The chloromethylketone protease inhibitor AAPF(CMK) also targets ATP-dependent helicases and SAP-domain proteins.
abstract: We have been studying a nuclear protease, which appears to be involved in cellular transformation, as well as in infections with high-risk human papillomaviruses (HPVs). This protease has a chymotrypsin-like substrate specificity and the chloromethylketone inhibitor AAPF(CMK) is a potent (and relatively selective) inhibitor of it. Recently, we have observed that AAPF(CMK) has potent effects in some model systems which appear not to be mediated by decreases in the nuclear protease. Here we show that AAPF(CMK) selectively reacts with ATP-dependent helicases as well as a limited spectrum of proteins in other DNA repair/chromatin remodeling nuclear complexes, including for example Cohesin complex components and proteins containing SAP-domains. In vitro, AAPF(CMK) selectively reacts with SV40 large T antigen, and inhibits its helicase activity.
authors.affiliation: Gittlen Cancer Research Foundation, Pennsylvania State University, Hershey, PA 17033, USA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Dhamne
authors.forename: David A
authors.initials: DA
authors.lastname: Drubin
authors.forename: Kimberly
authors.initials: K
authors.lastname: Duncan
authors.forename: M Judith
authors.initials: MJ
authors.lastname: Tevethia
authors.forename: Gary A
authors.initials: GA
authors.lastname: Clawson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004265:DNA Helicases / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000952:Antigens, Polyomavirus Transforming; D009842:Oligopeptides; D011480:Protease Inhibitors; C083541:succinyl-alanylalanyl-prolyl-phenylalanine chloromethylketone; D000255:Adenosine Triphosphate; D004265:DNA Helicases