{"product_id":"zoledronic-acid-inhibits-cancer-growth-9783639365443","title":"Zoledronic Acid Inhibits Cancer Growth","description":"The aminobisphosphonate zoledronic acid(ZOL) has elicited significant attention due to its remarkable anti-tumoral activity, though its detailed mechanism of action remains unclear. Here, we demonstrate the existence of a nuclear GSK3-NFATc2 stabilization pathway that promotes cancer growth in vitro and in vivo and serves as a bonafide target of ZOL. Specifically, the serine\/threonine kinase GSK3 stabilizes nuclear NFATc2 through phosphorylation of the serine-rich SP2 domain, thus protecting the transcription factor from E3-ubiquitin ligase HDM2 mediated proteolysis. ZOL disrupts this NFATc2 stabilization pathway through two mechanisms, namely GSK3 inhibition and induction of HDM2 activity. Upon nuclear accumulation, HDM2 targets unphosphorylated NFATc2 for ubiquitination at acceptor lysine residues K-684\/K-897 and hence labels the factor for subsequent proteasomal degradation. Conversely, mutagenesis induced constitutive serine phosphorylation of the SP2 domain prevents NFATc2 from HDM2 mediated ubiquitination and degradation by ZOL. In conclusion, this report demonstrates a critical role of the GSK3-HDM2 signaling loop in the regulation of NFATc2 protein stabili\u003cbr\u003e\u003cbr\u003e\u003cb\u003eAuthor:\u003c\/b\u003e \u003ca href=\"https:\/\/sureshotbooks-com.myshopify.com\/search?type=product%2Carticle%2Cpage\u0026amp;q=AUTH-5597054\"\u003eShiv Kishor Singh\u003c\/a\u003e, \u003ca href=\"https:\/\/sureshotbooks-com.myshopify.com\/search?type=product%2Carticle%2Cpage\u0026amp;q=AUTH-14735557\"\u003eGarima Singh\u003c\/a\u003e, \u003ca href=\"https:\/\/sureshotbooks-com.myshopify.com\/search?type=product%2Carticle%2Cpage\u0026amp;q=AUTH-14728965\"\u003eVolker Ellenrieder\u003c\/a\u003e\u003cbr\u003e\u003cb\u003ePublisher:\u003c\/b\u003e VDM Verlag\u003cbr\u003e\u003cb\u003ePublished:\u003c\/b\u003e 07\/08\/2011\u003cbr\u003e\u003cb\u003ePages:\u003c\/b\u003e 120\u003cbr\u003e\u003cb\u003eBinding Type:\u003c\/b\u003e Paperback\u003cbr\u003e\u003cb\u003eWeight:\u003c\/b\u003e 0.41lbs\u003cbr\u003e\u003cb\u003eSize:\u003c\/b\u003e 9.00h x 6.00w x 0.28d\u003cbr\u003e\u003cb\u003eISBN13:\u003c\/b\u003e 9783639365443\u003cbr\u003e\u003cb\u003eISBN10:\u003c\/b\u003e 3639365445\u003cbr\u003e\u003cb\u003eBISAC Categories:\u003c\/b\u003e\u003cbr\u003e- \u003ca href=\"https:\/\/sureshotbooks-com.myshopify.com\/search?type=product%2Carticle%2Cpage\u0026amp;q=CAT-SCI\"\u003eScience\u003c\/a\u003e | \u003ca href=\"https:\/\/sureshotbooks-com.myshopify.com\/search?type=product%2Carticle%2Cpage\u0026amp;q=BISAC-SCI007000\"\u003eLife Sciences | Biochemistry\u003c\/a\u003e\u003cbr\u003e\u003cp\u003e\u003ci\u003eThis title is not returnable\u003c\/i\u003e\u003cbr\u003e\u003c\/p\u003e","brand":"VDM Verlag","offers":[{"title":"Default Title","offer_id":44437230682349,"sku":"9783639365443","price":70.57,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0550\/8097\/6621\/products\/img_84254aa3-2d94-4395-9e5d-f1192b307986.jpg?v=1700123766","url":"https:\/\/sureshotbooks.com\/es\/products\/zoledronic-acid-inhibits-cancer-growth-9783639365443","provider":"SureShot Books Publishing LLC","version":"1.0","type":"link"}