The protein TAB2, known as a facultative component of the NCoR complex, was shown to shuttle NCoR to the cytoplasm in response to inflammatory signals, causing resistance to antiandrogen in prostate and antiestrogen in breast cancer cells. In addition, the role of Tab2 is studied in erbB4 signalling of neuronal precursors. The intracellular portion of erbB4 associates with Tab2 and corepressor NCoR to regulate the transcription of differentiation markers genes. On this way we have studied Tab2 as modulator of different pathways in two different cellular models, breast cancer cells and neuronal precursors. In tamoxifen resistant breast cancer cells, in all the clones retaining ERα expression, NCoR was aberrantly localized in the cytoplasm, similarly to what is observed in wild-type Tamoxifen-sensitive MCF7 cells after treatment with IL-1β. Following these observations, we directly assessed the role of TAB2 in NCoR delocalization, by down-regulating TAB2 in TAMR cells using specific siRNA. Downregulation of Tab2 was accompanied by recovery of NcoR nuclear localization and cell growth inhibition upon tamoxifen treatment, demonstrating the primary role of Tab2 in gene derepression in this system.. In the neuronal precursor lines ST14 the inibition of Tab2 with RNA interferance modulated the migration of different clones expressing the cleavable ERBB4 form. Tab2 was co-immunoprecipitated with ErbB4 after NRG1 stimulation. In addition, localization of Tab2 to the nucleus is induced by NRG1 treatment. Altogether these data support the notion of Tab2 as a main shuttle protein of corepressor complexes between cytosol and nucleus in response to different stimuli.
TAB2 as a shuttle protein of ERα and ErbB4 signalling
CUTRUPI, SANTINA;CAIZZI, LIVIA;REINERI, STEFANIA;GAMBAROTTA, Giovanna;PERROTEAU, Isabelle;DE BORTOLI, Michele
2009-01-01
Abstract
The protein TAB2, known as a facultative component of the NCoR complex, was shown to shuttle NCoR to the cytoplasm in response to inflammatory signals, causing resistance to antiandrogen in prostate and antiestrogen in breast cancer cells. In addition, the role of Tab2 is studied in erbB4 signalling of neuronal precursors. The intracellular portion of erbB4 associates with Tab2 and corepressor NCoR to regulate the transcription of differentiation markers genes. On this way we have studied Tab2 as modulator of different pathways in two different cellular models, breast cancer cells and neuronal precursors. In tamoxifen resistant breast cancer cells, in all the clones retaining ERα expression, NCoR was aberrantly localized in the cytoplasm, similarly to what is observed in wild-type Tamoxifen-sensitive MCF7 cells after treatment with IL-1β. Following these observations, we directly assessed the role of TAB2 in NCoR delocalization, by down-regulating TAB2 in TAMR cells using specific siRNA. Downregulation of Tab2 was accompanied by recovery of NcoR nuclear localization and cell growth inhibition upon tamoxifen treatment, demonstrating the primary role of Tab2 in gene derepression in this system.. In the neuronal precursor lines ST14 the inibition of Tab2 with RNA interferance modulated the migration of different clones expressing the cleavable ERBB4 form. Tab2 was co-immunoprecipitated with ErbB4 after NRG1 stimulation. In addition, localization of Tab2 to the nucleus is induced by NRG1 treatment. Altogether these data support the notion of Tab2 as a main shuttle protein of corepressor complexes between cytosol and nucleus in response to different stimuli.
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