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The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the antiapoptotic function of BAG-1 protein in colorectal tumour cells: Rb increases nuclear localisation and function of BAG-1

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@article{0e00d49a436444df8ed39ff2184c8355,
title = "The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the antiapoptotic function of BAG-1 protein in colorectal tumour cells: Rb increases nuclear localisation and function of BAG-1",
abstract = "Although the retinoblastoma-susceptibility gene RB1 is inactivated in a wide range of human tumours, in colorectal cancer, the retinoblastoma protein (Rb) function is often preserved and the RB locus even amplified. Importantly, we have previously shown that Rb interacts with the anti-apoptotic Bcl-2 associated athanogene 1 (BAG-1) protein, which is highly expressed in colorectal carcinogenesis. Here we show for the first time that Rb expression is critical for BAG-1 anti-apoptotic activity in colorectal tumour cells. We demonstrate that Rb expression not only increases the nuclear localisation of the anti-apoptotic BAG-1 protein, but that expression of Rb is required for inhibition of apoptosis by BAG-1 both in a c-irradiated Saos-2 osteosarcoma cell line and colorectal adenoma and carcinoma cell lines. Further, consistent with the fact that nuclear BAG-1 has previously been shown to promote cell survival through increasing nuclear factor (NF)-jB activity, we demonstrate that the ability of BAG-1 to promote NF-jB activity is significantly inhibited by repression of Rb expression. Taken together, data presented suggest a novel function for the Rb, promoting cell survival through regulating the function of BAG-1. As BAG-1 is highly expressed in the majority of colorectal tumours, targeting the Rb–BAG-1 complex to promote apoptosis has exciting potential for future therapeutic development.",
keywords = "BAG-1; Rb; NF-kB; apoptosis; colorectal cancer; osteosarcoma",
author = "Collard, {Tracey J} and Urban, {Bettina C} and Patsos, {Helena A} and Angela Hague and Christos Paraskeva and Williams, {Ann C} and PA Townsend",
year = "2012",
month = "10",
day = "11",
doi = "10.1038/cddis.2012.142",
language = "English",
volume = "3",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Springer Nature",

}

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TY - JOUR

T1 - The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the antiapoptotic function of BAG-1 protein in colorectal tumour cells

T2 - Rb increases nuclear localisation and function of BAG-1

AU - Collard, Tracey J

AU - Urban, Bettina C

AU - Patsos, Helena A

AU - Hague, Angela

AU - Paraskeva, Christos

AU - Williams, Ann C

AU - Townsend, PA

PY - 2012/10/11

Y1 - 2012/10/11

N2 - Although the retinoblastoma-susceptibility gene RB1 is inactivated in a wide range of human tumours, in colorectal cancer, the retinoblastoma protein (Rb) function is often preserved and the RB locus even amplified. Importantly, we have previously shown that Rb interacts with the anti-apoptotic Bcl-2 associated athanogene 1 (BAG-1) protein, which is highly expressed in colorectal carcinogenesis. Here we show for the first time that Rb expression is critical for BAG-1 anti-apoptotic activity in colorectal tumour cells. We demonstrate that Rb expression not only increases the nuclear localisation of the anti-apoptotic BAG-1 protein, but that expression of Rb is required for inhibition of apoptosis by BAG-1 both in a c-irradiated Saos-2 osteosarcoma cell line and colorectal adenoma and carcinoma cell lines. Further, consistent with the fact that nuclear BAG-1 has previously been shown to promote cell survival through increasing nuclear factor (NF)-jB activity, we demonstrate that the ability of BAG-1 to promote NF-jB activity is significantly inhibited by repression of Rb expression. Taken together, data presented suggest a novel function for the Rb, promoting cell survival through regulating the function of BAG-1. As BAG-1 is highly expressed in the majority of colorectal tumours, targeting the Rb–BAG-1 complex to promote apoptosis has exciting potential for future therapeutic development.

AB - Although the retinoblastoma-susceptibility gene RB1 is inactivated in a wide range of human tumours, in colorectal cancer, the retinoblastoma protein (Rb) function is often preserved and the RB locus even amplified. Importantly, we have previously shown that Rb interacts with the anti-apoptotic Bcl-2 associated athanogene 1 (BAG-1) protein, which is highly expressed in colorectal carcinogenesis. Here we show for the first time that Rb expression is critical for BAG-1 anti-apoptotic activity in colorectal tumour cells. We demonstrate that Rb expression not only increases the nuclear localisation of the anti-apoptotic BAG-1 protein, but that expression of Rb is required for inhibition of apoptosis by BAG-1 both in a c-irradiated Saos-2 osteosarcoma cell line and colorectal adenoma and carcinoma cell lines. Further, consistent with the fact that nuclear BAG-1 has previously been shown to promote cell survival through increasing nuclear factor (NF)-jB activity, we demonstrate that the ability of BAG-1 to promote NF-jB activity is significantly inhibited by repression of Rb expression. Taken together, data presented suggest a novel function for the Rb, promoting cell survival through regulating the function of BAG-1. As BAG-1 is highly expressed in the majority of colorectal tumours, targeting the Rb–BAG-1 complex to promote apoptosis has exciting potential for future therapeutic development.

KW - BAG-1; Rb; NF-kB; apoptosis; colorectal cancer; osteosarcoma

U2 - 10.1038/cddis.2012.142

DO - 10.1038/cddis.2012.142

M3 - Article

VL - 3

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

M1 - e408

ER -