TY - JOUR
T1 - Multicolor monitoring of the proteasomes catalytic signature
AU - Priestman, Melanie A.
AU - Wang, Qunzhao
AU - Jernigan, Finith E.
AU - Chowdhury, Ruma
AU - Schmidt, Marion
AU - Lawrence, David S.
N1 - Publisher Copyright:
© 2014 American Chemical Society.
PY - 2015/2/20
Y1 - 2015/2/20
N2 - The proteasome, a validated anticancer target, participates in an array of biochemical activities, which range from the proteolysis of defective proteins to antigen presentation. We report the preparation of biochemically and photophysically distinct green, red, and far-red real-time sensors designed to simultaneously monitor the proteasomes chymotrypsin-, trypsin-, and caspase-like activities, respectively. These sensors were employed to assess the effect of simultaneous multiple active site catalysis on the kinetic properties of the individual subunits. Furthermore, we have found that the catalytic signature of the proteasome varies depending on the source, cell type, and disease state. Trypsin-like activity is more pronounced in yeast than in mammals, whereas chymotrypsin-like activity is the only activity detectable in B-cells (unlike other mammalian cells). Furthermore, chymotrypsin-like activity is more prominent in transformed B cells relative to their counterparts from healthy donors.
AB - The proteasome, a validated anticancer target, participates in an array of biochemical activities, which range from the proteolysis of defective proteins to antigen presentation. We report the preparation of biochemically and photophysically distinct green, red, and far-red real-time sensors designed to simultaneously monitor the proteasomes chymotrypsin-, trypsin-, and caspase-like activities, respectively. These sensors were employed to assess the effect of simultaneous multiple active site catalysis on the kinetic properties of the individual subunits. Furthermore, we have found that the catalytic signature of the proteasome varies depending on the source, cell type, and disease state. Trypsin-like activity is more pronounced in yeast than in mammals, whereas chymotrypsin-like activity is the only activity detectable in B-cells (unlike other mammalian cells). Furthermore, chymotrypsin-like activity is more prominent in transformed B cells relative to their counterparts from healthy donors.
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U2 - 10.1021/cb5007322
DO - 10.1021/cb5007322
M3 - Article
AN - SCOPUS:84923319516
SN - 1554-8929
VL - 10
SP - 433
EP - 440
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 2
ER -