Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer

Hee June Choi; Ji Min Lee; Hyunkyung Kim; Hye Jin Nam; Hi Jai R. Shin; Dongha Kim; Enyoung Ko; Dong Young Noh; Keun Il Kim; Jung Hwa Kim; Sung Hee Baek

doi:10.1016/j.bbrc.2010.08.084

Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer

Hee June Choi, Ji Min Lee, Hyunkyung Kim, Hye Jin Nam, Hi Jai R. Shin, Dongha Kim, Enyoung Ko, Dong Young Noh, Keun Il Kim, Jung Hwa Kim, Sung Hee Baek

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.

Original language	English
Pages (from-to)	396-402
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	400
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2010.08.084
Publication status	Published - 2010 Sept
Externally published	Yes

Bibliographical note

Funding Information:
pcDNA-Flag-Bcl3 WT, ΔC, and ΔNΔC constructs were kindly given by Alain Chariot and pcDNA4-HA-CtBP1 was provided by Hong-Duk Youn. We thank Dr. Tohru Natsume for the mass spectrometric analysis and Young Eun Kwon, Ik Soo Kim, and Min Kyung Lee for technical assistance. This CRI work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (Chromatin Dynamics Research Center , 2009-0081563 ) to S.H.B., by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (MOST) ( 2008-0060604 ) to J.H.K., by the Ubiquitome Research Program ( 2008-00983 ) to K.I.K. from the NRF grant funded by the MEST of Korea , and by the Brain Korea 21 fellowship and Seoul Science Fellowship given to H.J.C., J.M.L, H.K., and H.J.N.

Keywords

Apoptosis
Bcl3
Cancer
CtBP1
Ubiquitination

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2010.08.084

Cite this

Choi, H. J., Lee, J. M., Kim, H., Nam, H. J., Shin, H. J. R., Kim, D., Ko, E., Noh, D. Y., Kim, K. I., Kim, J. H., & Baek, S. H. (2010). Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer. Biochemical and biophysical research communications, 400(3), 396-402. https://doi.org/10.1016/j.bbrc.2010.08.084

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abstract = "B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.",

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author = "Choi, {Hee June} and Lee, {Ji Min} and Hyunkyung Kim and Nam, {Hye Jin} and Shin, {Hi Jai R.} and Dongha Kim and Enyoung Ko and Noh, {Dong Young} and Kim, {Keun Il} and Kim, {Jung Hwa} and Baek, {Sung Hee}",

note = "Funding Information: pcDNA-Flag-Bcl3 WT, ΔC, and ΔNΔC constructs were kindly given by Alain Chariot and pcDNA4-HA-CtBP1 was provided by Hong-Duk Youn. We thank Dr. Tohru Natsume for the mass spectrometric analysis and Young Eun Kwon, Ik Soo Kim, and Min Kyung Lee for technical assistance. This CRI work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (Chromatin Dynamics Research Center , 2009-0081563 ) to S.H.B., by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (MOST) ( 2008-0060604 ) to J.H.K., by the Ubiquitome Research Program ( 2008-00983 ) to K.I.K. from the NRF grant funded by the MEST of Korea , and by the Brain Korea 21 fellowship and Seoul Science Fellowship given to H.J.C., J.M.L, H.K., and H.J.N.",

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T1 - Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer

AU - Choi, Hee June

AU - Lee, Ji Min

AU - Kim, Hyunkyung

AU - Nam, Hye Jin

AU - Shin, Hi Jai R.

AU - Kim, Dongha

AU - Ko, Enyoung

AU - Noh, Dong Young

AU - Kim, Keun Il

AU - Kim, Jung Hwa

AU - Baek, Sung Hee

N1 - Funding Information: pcDNA-Flag-Bcl3 WT, ΔC, and ΔNΔC constructs were kindly given by Alain Chariot and pcDNA4-HA-CtBP1 was provided by Hong-Duk Youn. We thank Dr. Tohru Natsume for the mass spectrometric analysis and Young Eun Kwon, Ik Soo Kim, and Min Kyung Lee for technical assistance. This CRI work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (Chromatin Dynamics Research Center , 2009-0081563 ) to S.H.B., by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (MOST) ( 2008-0060604 ) to J.H.K., by the Ubiquitome Research Program ( 2008-00983 ) to K.I.K. from the NRF grant funded by the MEST of Korea , and by the Brain Korea 21 fellowship and Seoul Science Fellowship given to H.J.C., J.M.L, H.K., and H.J.N.

PY - 2010/9

Y1 - 2010/9

N2 - B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.

AB - B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.

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SN - 0006-291X

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JO - Biochemical and biophysical research communications

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IS - 3

ER -

Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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