Role for Hes1-Induced Phosphorylation in Groucho-Mediated Transcriptional Repression
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| Published in | Molecular and Cellular Biology Vol. 22; no. 2; pp. 389 - 399 |
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| Format | Journal Article |
| Language | English |
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American Society for Microbiology
01.01.2002
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| AbstractList | Transcriptional corepressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of developmental pathways in both invertebrates and vertebrates. They form transcription repression complexes with members of several DNA-binding protein families and participate in the regulation of the expression of numerous genes. Despite their pleiotropic roles, little is known about the mechanisms that regulate the functions of Gro/TLE proteins. It is shown here that Gro/TLEs become hyperphosphorylated in response to neural cell differentiation and interaction with the DNA-binding cofactor Hairy/Enhancer of split 1 (Hes1). Hyperphosphorylation of Gro/TLEs is correlated with a tight association with the nuclear compartment through interaction with chromatin, suggesting that hyperphosphorylated Gro/TLEs may mediate transcriptional repression via chromatin remodeling mechanisms. Pharmacological inhibition of protein kinase CK2 reduces the Hes1-induced hyperphosphorylation of Gro/TLEs and causes a decrease in the chromatin association of the latter. Moreover, the transcription repression activity of Gro/TLEs is reduced by protein kinase CK2 inhibition. Consistent with these observations, Gro/TLEs are phosphorylated in vitro by purified protein kinase CK2. Taken together, these results implicate protein kinase CK2 in Gro/TLE functions. They suggest further that this kinase is involved in a hyperphosphorylation mechanism activated by Hes1 that promotes the transcription repression functions of Hes1-Gro/TLE protein complexes. Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB Transcriptional corepressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of developmental pathways in both invertebrates and vertebrates. They form transcription repression complexes with members of several DNA-binding protein families and participate in the regulation of the expression of numerous genes. Despite their pleiotropic roles, little is known about the mechanisms that regulate the functions of Gro/TLE proteins. It is shown here that Gro/TLEs become hyperphosphorylated in response to neural cell differentiation and interaction with the DNA-binding cofactor Hairy/Enhancer of split 1 (Hes1). Hyperphosphorylation of Gro/TLEs is correlated with a tight association with the nuclear compartment through interaction with chromatin, suggesting that hyperphosphorylated Gro/TLEs may mediate transcriptional repression via chromatin remodeling mechanisms. Pharmacological inhibition of protein kinase CK2 reduces the Hes1-induced hyperphosphorylation of Gro/TLEs and causes a decrease in the chromatin association of the latter. Moreover, the transcription repression activity of Gro/TLEs is reduced by protein kinase CK2 inhibition. Consistent with these observations, Gro/TLEs are phosphorylated in vitro by purified protein kinase CK2. Taken together, these results implicate protein kinase CK2 in Gro/TLE functions. They suggest further that this kinase is involved in a hyperphosphorylation mechanism activated by Hes1 that promotes the transcription repression functions of Hes1-Gro/TLE protein complexes.Transcriptional corepressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of developmental pathways in both invertebrates and vertebrates. They form transcription repression complexes with members of several DNA-binding protein families and participate in the regulation of the expression of numerous genes. Despite their pleiotropic roles, little is known about the mechanisms that regulate the functions of Gro/TLE proteins. It is shown here that Gro/TLEs become hyperphosphorylated in response to neural cell differentiation and interaction with the DNA-binding cofactor Hairy/Enhancer of split 1 (Hes1). Hyperphosphorylation of Gro/TLEs is correlated with a tight association with the nuclear compartment through interaction with chromatin, suggesting that hyperphosphorylated Gro/TLEs may mediate transcriptional repression via chromatin remodeling mechanisms. Pharmacological inhibition of protein kinase CK2 reduces the Hes1-induced hyperphosphorylation of Gro/TLEs and causes a decrease in the chromatin association of the latter. Moreover, the transcription repression activity of Gro/TLEs is reduced by protein kinase CK2 inhibition. Consistent with these observations, Gro/TLEs are phosphorylated in vitro by purified protein kinase CK2. Taken together, these results implicate protein kinase CK2 in Gro/TLE functions. They suggest further that this kinase is involved in a hyperphosphorylation mechanism activated by Hes1 that promotes the transcription repression functions of Hes1-Gro/TLE protein complexes. |
| Author | Junaid Husain Stefano Stifani Keith W. McLarren Hugh N. Nuthall |
| AuthorAffiliation | Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada |
| AuthorAffiliation_xml | – name: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada |
| Author_xml | – sequence: 1 givenname: Hugh N. surname: Nuthall fullname: Nuthall, Hugh N. organization: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal – sequence: 2 givenname: Junaid surname: Husain fullname: Husain, Junaid organization: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal – sequence: 3 givenname: Keith W. surname: McLarren fullname: McLarren, Keith W. organization: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal – sequence: 4 givenname: Stefano surname: Stifani fullname: Stifani, Stefano email: stefano.stifani@mcgill.ca organization: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11756536$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Present address: Department of Craniofacial Development, King’s College, London, United Kingdom. Corresponding author. Mailing address: Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada. Phone: (514) 398-3946. Fax: (514) 398-1319. E-mail: stefano.stifani@mcgill.ca. |
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Mendeley... Transcriptional corepressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate a number of developmental pathways in both... |
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| StartPage | 389 |
| SubjectTerms | Animals Basic Helix-Loop-Helix Transcription Factors Casein Kinase II Cell Differentiation Cell Nucleus - metabolism Cells, Cultured Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Enzyme Inhibitors - pharmacology Groucho protein Hes1 protein Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Mice Models, Biological Neurons - cytology Neurons - metabolism Phosphorylation Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism TLE protein Transcription Factor HES-1 Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic Transcriptional Regulation Transfection |
| Title | Role for Hes1-Induced Phosphorylation in Groucho-Mediated Transcriptional Repression |
| URI | http://mcb.asm.org/content/22/2/389.abstract https://www.tandfonline.com/doi/abs/10.1128/MCB.22.2.389-399.2002 https://www.ncbi.nlm.nih.gov/pubmed/11756536 https://www.proquest.com/docview/18157722 https://www.proquest.com/docview/71351508 https://pubmed.ncbi.nlm.nih.gov/PMC139746 |
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