Cks1 proteasomal degradation is induced by inhibiting Hsp90-mediated chaperoning in cancer cells

Abstract

We conclude that perturbing the Hsp90 pathway could provide a useful therapeutic strategy in tumors driven by Cks1 overexpression.

p27 Kip1 signaling: Transcriptional and post-translational regulation

“…Benzoquinone ansamycin 17-allylamino geldanamycin (17-AAG) is a proteasome inhibitor that is able to stabilize p27 Kip1 by depletion of Cks1, the bridge between SKP2 and p27 Kip1 (Khattar et al 2014). Treatment of colon carcinoma cells with 17-AAG resulted in G 1 cell cycle arrest (Khattar et al 2014).…”

“…Benzoquinone ansamycin 17-allylamino geldanamycin (17-AAG) is a proteasome inhibitor that is able to stabilize p27 Kip1 by depletion of Cks1, the bridge between SKP2 and p27 Kip1 (Khattar et al 2014). Treatment of colon carcinoma cells with 17-AAG resulted in G 1 cell cycle arrest (Khattar et al 2014). Restoring p27 Kip1 levels by influencing its gene expression regulators and rectifying p27 Kip1 mislocalization via targeting SRC, CRM1 and PIM, may also provide new avenue for treatment of a variety of cancers.…”

Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion

“…28,29 MG-132 is a reversible and cell-permeable inhibitor that primarily acts on the chymotrypsin-like site in the β subunit of the proteasome. Epoximicin is a highly potent, irreversible, and one of the most specific proteasome inhibitors that also primarily reacts with the chymotrypsin-like site.…”

“…Epoximicin is a highly potent, irreversible, and one of the most specific proteasome inhibitors that also primarily reacts with the chymotrypsin-like site. 28,29 MG-132 is a reversible and cell-permeable inhibitor that primarily acts on the chymotrypsin-like site in the β subunit of the proteasome. 30 293T cells were transfected with HA-tagged BMP2 expression plasmid, pCMV3-HA-BMP2.…”

A plant-made cholera toxin B subunit enhances mucosal wound healing and protects against ulcerative colitis and colon cancer.

“…Hspa5, Hspa8, Hsp90aa1, and Stip1, which are implicated in the progression of colon cancer, were significantly suppressed in several pathways (89)(90)(91)(92)(93)(94). To confirm microarray data, quantitative real-time-PCR (qPCR) was performed on selected induced (i.e., collagen, decorin, mitogen-activated protein KKKK 4, and tissue inhibitor of metalloproteinase 4), suppressed (malate dehydrogenase 1 and angiogenin), or unaltered genes (ATP binding cassette and SMAD family member 6) and a high agreement between microarray and qPCR results was obtained ( Fig.…”