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Endocrine-Related Cancer 14 (1) 153-167    DOI: 10.1677/ERC-06-0020
Copyright © 2007 by the Society for Endocrinology.
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Role of ERß palmitoylation in the inhibition of human colon cancer cell proliferation

Paola Galluzzo, Francesco Caiazza, Sandra Moreno and Maria Marino

Department of Biology, University ‘Roma Tre’, Viale G Marconi, 446,I-00146 Roma, Italy

(Requests for offprints should be addressed to M Marino; Email: m.marino{at}uniroma3.it)

The cellular functions regulated by 17ß-estradiol (E2) start after the hormone binds to its receptors (i.e., ER{alpha} and ERß ). These act as ligand-dependent transcription factor transactivating target genes. In addition, E2 induces non-genomic actions, whose activation is triggered by a fraction of the ERs localized at the plasma membrane. Palmitoylation allows ER{alpha} to localize at the plasma membrane, to associate with caveolin-1, and, upon E2 stimulation, to activate rapid signals relevant for cell proliferation. The existence of a mechanism, which allows ERß localization at the plasma membrane and its putative role in anti-proliferative E2 effects is completely unknown. Here, the susceptibility of ERß to undergo palmitoylation and the role played by this process has been analyzed in DLD-1 containing endogenous ERß or in HeLa cells transiently transfected with ERß or ER{alpha} expression vectors. As for ER{alpha} , palmitoylation is necessary for ERß localization at the plasma membrane and its association with caveolin-1 but, in contrast to ER{alpha} , the E2 binding increases ERß association with caveolin-1 and the p38 member of MAPK family. Moreover, the palmitoyl acyl transferase (PAT) inhibitor blocks the ability of ERß –E2 complex to activate p38 impairing the receptor-dependent activation of downstream proapoptotic cascade (i.e., caspase-3 activation and poly(ADP-ribose)polymerase (PARP) cleavage). Consequently, palmitoylation must be considered to be a molecular device for ERß , which allows these receptors to interact with the plasma membrane and to regulate E2-induced non-genomic functions relevant to the anti-proliferative effect of this hormone.




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P. Galluzzo, P. Ascenzi, P. Bulzomi, and M. Marino
The Nutritional Flavanone Naringenin Triggers Antiestrogenic Effects by Regulating Estrogen Receptor {alpha}-Palmitoylation
Endocrinology, May 1, 2008; 149(5): 2567 - 2575.
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