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Wienecke R , Maize JC , Shoarinejad F , Vass WC , Reed J , Bonifacino JS , Resau JH , deGunzburg J , Yeung RS , DeClue JE
Co-localization of the TSC2 product tuberin with its target Rap1 in the golgi apparatus
Oncogene. 1996 Sep 5;13(5) :913-923
PMID: ISI:A1996VG76600004   
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Abstract
Tuberin is the protein product of the tuberous sclerosis-2 (TSC2) gene, which is associated with tuberous sclerosis (TSC), a human genetic syndrome characterized by the development of tumors in a variety of tissues, We have previously shown that tuberin is a widely expressed 180 kDa protein which exhibits specific GTPase activating activity in vitro towards the Ras- related Rap1 study we have used affinity-purified antibodies against tuberin to analyse its expression in human and rat tissues and to examine its subcellular localization, Tuberin expression was detected in all adult human tissues tested, with the highest levels found in brain, heart and kidney, organs that are commonly affected in TSC patients, By contrast, in adult rats the highest levels of tuberin were found in brain, liver and testis, Indirect immunofluorescence of tuberin in various cultured cell lines revealed a punctate, mostly perinuclear staining pattern, Double-indirect immunofluorescence analysis sera and anti-tuberin sera and antisera against known Golgi markers (mannosidase-II and furin) revealed that the staining of tuberin was consistent with its localization in the stacks of the Golgi apparatus, In support of this, treatment of cells with brefeldin A, a drug known to cause disassembly of the Golgi apparatus: abolished the perinuclear staining of tuberin, Moreover, conventional and confocal immunofluorescence demonstrated co-localization of tuberin with Rap1, which has previously been localized to the Golgi apparatus, The colocalization of tuberin and Rap1 in vivo strengthens the likelihood that the in vitro catalytic activity of tuberin toward Rap1 plays a physiologically relevant role in the tumor suppressor function of tuberin.
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Times Cited: 57 English Article VG766 ONCOGENE