The cellular functions regulated by 17b-estradiol (E2) start after the hormone binds to its receptors (i.e., ERa and ERb). 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 ERa 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 ERb localization at the plasma membrane and its putative role in anti-proliferative E2 effects is completely unknown. Here, the susceptibility of ERb to undergo palmitoylation and the role played by this process has been analyzed in DLD-1 containing endogenous ERb or in HeLa cells transiently transfected with ERb or ERa expression vectors. As for ERa, palmitoylation is necessary for ERb localization at the plasma membrane and its association with caveolin-1 but, in contrast to ERa, the E2 binding increases ERb association with caveolin-1 and the p38 member of MAPK family. Moreover, the palmitoyl acyl transferase (PAT) inhibitor blocks the ability of ERb–E2 complex to activate p38 impairing the receptor-dependent activation of downstream pro-apoptotic cascade (i.e., caspase- 3 activation and poly(ADP-ribose)polymerase (PARP) cleavage). Consequently, palmitoylation must be considered to be a molecular device for ERb, which allows these receptors to interact with the plasma membrane and to regulate E2-induced non-genomic functions relevant to the antiproliferative effect of this hormone.
|Titolo:||Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation|
|Data di pubblicazione:||2007|
|Citazione:||Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation / Galluzzo P; Caiazza F; Moreno S; Marino M. - In: ENDOCRINE-RELATED CANCER. - ISSN 1351-0088. - 14(2007), pp. 153-167.|
|Appare nelle tipologie:||1.1 Articolo in rivista|