The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences

The leukemia-associated fusion protein MN1-TEL combines the transcription-activating domains of MN1 with the DNA-binding domain of the transcriptional repressor TEL. Quantitative photobleaching experiments revealed that ∼20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirec...

Descripción completa

Detalles Bibliográficos
Autores principales: ter Haar, W. Martijn, Meester-Smoor, Magda A., van Wely, Karel H. M., Schot, Claudia C. M. M., Janssen, Marjolein J. F. W., Geverts, Bart, Bonten, Jacqueline, Grosveld, Gerard C., Houtsmuller, Adriaan B., Zwarthoff, Ellen C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458806/
https://www.ncbi.nlm.nih.gov/pubmed/23049943
http://dx.doi.org/10.1371/journal.pone.0046085
_version_ 1782244705658994688
author ter Haar, W. Martijn
Meester-Smoor, Magda A.
van Wely, Karel H. M.
Schot, Claudia C. M. M.
Janssen, Marjolein J. F. W.
Geverts, Bart
Bonten, Jacqueline
Grosveld, Gerard C.
Houtsmuller, Adriaan B.
Zwarthoff, Ellen C.
author_facet ter Haar, W. Martijn
Meester-Smoor, Magda A.
van Wely, Karel H. M.
Schot, Claudia C. M. M.
Janssen, Marjolein J. F. W.
Geverts, Bart
Bonten, Jacqueline
Grosveld, Gerard C.
Houtsmuller, Adriaan B.
Zwarthoff, Ellen C.
author_sort ter Haar, W. Martijn
collection PubMed
description The leukemia-associated fusion protein MN1-TEL combines the transcription-activating domains of MN1 with the DNA-binding domain of the transcriptional repressor TEL. Quantitative photobleaching experiments revealed that ∼20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, ∼50% of the MN1-TEL fusion protein was immobile with much longer binding times than unfused MN1 and TEL. MN1-TEL immobilisation was not observed when the TEL DNA-binding domain was disrupted, suggesting that MN1-TEL stably occupies TEL recognition sequences, preventing binding of factors required for proper transcription regulation, which may contribute to leukemogenesis.
format Online
Article
Text
id pubmed-3458806
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-34588062012-10-03 The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences ter Haar, W. Martijn Meester-Smoor, Magda A. van Wely, Karel H. M. Schot, Claudia C. M. M. Janssen, Marjolein J. F. W. Geverts, Bart Bonten, Jacqueline Grosveld, Gerard C. Houtsmuller, Adriaan B. Zwarthoff, Ellen C. PLoS One Research Article The leukemia-associated fusion protein MN1-TEL combines the transcription-activating domains of MN1 with the DNA-binding domain of the transcriptional repressor TEL. Quantitative photobleaching experiments revealed that ∼20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, ∼50% of the MN1-TEL fusion protein was immobile with much longer binding times than unfused MN1 and TEL. MN1-TEL immobilisation was not observed when the TEL DNA-binding domain was disrupted, suggesting that MN1-TEL stably occupies TEL recognition sequences, preventing binding of factors required for proper transcription regulation, which may contribute to leukemogenesis. Public Library of Science 2012-09-26 /pmc/articles/PMC3458806/ /pubmed/23049943 http://dx.doi.org/10.1371/journal.pone.0046085 Text en © 2012 ter Haar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
ter Haar, W. Martijn
Meester-Smoor, Magda A.
van Wely, Karel H. M.
Schot, Claudia C. M. M.
Janssen, Marjolein J. F. W.
Geverts, Bart
Bonten, Jacqueline
Grosveld, Gerard C.
Houtsmuller, Adriaan B.
Zwarthoff, Ellen C.
The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title_full The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title_fullStr The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title_full_unstemmed The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title_short The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
title_sort leukemia-associated fusion protein mn1-tel blocks tel-specific recognition sequences
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458806/
https://www.ncbi.nlm.nih.gov/pubmed/23049943
http://dx.doi.org/10.1371/journal.pone.0046085
work_keys_str_mv AT terhaarwmartijn theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT meestersmoormagdaa theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT vanwelykarelhm theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT schotclaudiacmm theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT janssenmarjoleinjfw theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT gevertsbart theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT bontenjacqueline theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT grosveldgerardc theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT houtsmulleradriaanb theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT zwarthoffellenc theleukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT terhaarwmartijn leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT meestersmoormagdaa leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT vanwelykarelhm leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT schotclaudiacmm leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT janssenmarjoleinjfw leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT gevertsbart leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT bontenjacqueline leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT grosveldgerardc leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT houtsmulleradriaanb leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences
AT zwarthoffellenc leukemiaassociatedfusionproteinmn1telblockstelspecificrecognitionsequences

Ejemplares similares