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Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins

BACKGROUND: CtBP1 and CtBP2 are transcriptional co-repressors that modulate the activity of a large number of transcriptional repressors via the recruitment of chromatin modifiers. Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-β and Wnt signalling...

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Autores principales: Bergman, Lee M, Morris, Laila, Darley, Matthew, Mirnezami, Alexander H, Gunatilake, Samal C, Blaydes, Jeremy P
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592084/
https://www.ncbi.nlm.nih.gov/pubmed/16999872
http://dx.doi.org/10.1186/1471-2121-7-35
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author Bergman, Lee M
Morris, Laila
Darley, Matthew
Mirnezami, Alexander H
Gunatilake, Samal C
Blaydes, Jeremy P
author_facet Bergman, Lee M
Morris, Laila
Darley, Matthew
Mirnezami, Alexander H
Gunatilake, Samal C
Blaydes, Jeremy P
author_sort Bergman, Lee M
collection PubMed
description BACKGROUND: CtBP1 and CtBP2 are transcriptional co-repressors that modulate the activity of a large number of transcriptional repressors via the recruitment of chromatin modifiers. Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-β and Wnt signalling pathways and cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A. CtBP1 and CtBP2 are highly similar proteins, although evidence is emerging that their activity can be differentially regulated, particularly through the control of their subcellular localisation. CtBP2s from diverse species contain a unique N-terminus, absent in CtBP1 that plays a key role in controlling the nuclear-cytoplasmic distribution of the protein. RESULTS: Here we show that amino acids (a.a.) 4–14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution in cell lines of diverse origins. Whilst this sequence contains similarity to known nuclear localisation motifs, it cannot drive nuclear localisation of a heterologous protein, but rather has been shown to function as a p300 acetyltransferase-dependent nuclear retention sequence. Here we define the region of CtBP2 required to co-operate with a.a. 4–14 to promote CtBP2 nuclear accumulation as being within a.a. 1–119. In addition, we show that a.a. 120–445 of CtBP2 can also promote CtBP2 nuclear accumulation, independently of a.a. 4–14. Finally, CtBP1 and CtBP2 can form heterodimers, and we show that the interaction with CtBP2 is one mechanism whereby CtBP1 can be recruited to the nucleus. CONCLUSION: Together, these findings represent key distinctions in the regulation of the functions of CtBP family members that may have important implications as to their roles in development, and cell differentiation and survival.
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spelling pubmed-15920842006-10-05 Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins Bergman, Lee M Morris, Laila Darley, Matthew Mirnezami, Alexander H Gunatilake, Samal C Blaydes, Jeremy P BMC Cell Biol Research Article BACKGROUND: CtBP1 and CtBP2 are transcriptional co-repressors that modulate the activity of a large number of transcriptional repressors via the recruitment of chromatin modifiers. Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-β and Wnt signalling pathways and cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A. CtBP1 and CtBP2 are highly similar proteins, although evidence is emerging that their activity can be differentially regulated, particularly through the control of their subcellular localisation. CtBP2s from diverse species contain a unique N-terminus, absent in CtBP1 that plays a key role in controlling the nuclear-cytoplasmic distribution of the protein. RESULTS: Here we show that amino acids (a.a.) 4–14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution in cell lines of diverse origins. Whilst this sequence contains similarity to known nuclear localisation motifs, it cannot drive nuclear localisation of a heterologous protein, but rather has been shown to function as a p300 acetyltransferase-dependent nuclear retention sequence. Here we define the region of CtBP2 required to co-operate with a.a. 4–14 to promote CtBP2 nuclear accumulation as being within a.a. 1–119. In addition, we show that a.a. 120–445 of CtBP2 can also promote CtBP2 nuclear accumulation, independently of a.a. 4–14. Finally, CtBP1 and CtBP2 can form heterodimers, and we show that the interaction with CtBP2 is one mechanism whereby CtBP1 can be recruited to the nucleus. CONCLUSION: Together, these findings represent key distinctions in the regulation of the functions of CtBP family members that may have important implications as to their roles in development, and cell differentiation and survival. BioMed Central 2006-09-25 /pmc/articles/PMC1592084/ /pubmed/16999872 http://dx.doi.org/10.1186/1471-2121-7-35 Text en Copyright © 2006 Bergman et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bergman, Lee M
Morris, Laila
Darley, Matthew
Mirnezami, Alexander H
Gunatilake, Samal C
Blaydes, Jeremy P
Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title_full Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title_fullStr Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title_full_unstemmed Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title_short Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins
title_sort role of the unique n-terminal domain of ctbp2 in determining the subcellular localisation of ctbp family proteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592084/
https://www.ncbi.nlm.nih.gov/pubmed/16999872
http://dx.doi.org/10.1186/1471-2121-7-35
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