Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch... Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors Lizi Wu 1 , 2 , Tao Sun 2 , 3 , Karla Kobayashi 1 , 2 , Ping Gao 1 , 2 and James D. Griffin 1 , 2 , * 1 Departments of Medical Oncology 3 Pediatric Oncology, Dana-Farber Cancer Institute 2 Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 ABSTRACT The molecular mechanisms by which Notch receptors induce diverse biological responses are not fully understood. We recently cloned a mammalian homologue of the Mastermind gene of Drosophila melanogaster , MAML1 (Mastermind-like-1 molecule) and determined that it functions as a transcriptional coactivator for Notch receptors. In this report, we characterize two additional genes in this Mastermind-like gene family: MAML2 and MAML3. The three MAML genes are widely expressed in adult tissues but exhibit distinct expression patterns in mouse early spinal cord development. All MAML proteins localize to nuclear bodies, share a conserved basic domain in their N termini that binds to the ankyrin repeat domain of Notch, and contain a transcriptional activation domain in their C termini. Moreover, as determined by using coimmunoprecipitation assays, each MAML protein was found to be capable of forming a multiprotein complex with the intracellular domain of each Notch receptor (ICN1 to -4) and CSL in vivo. However, MAML3 bound less efficiently to the ankyrin repeat domain of Notch1. Also, in U20S cells, whereas MAML1 and MAML2 functioned efficiently as coactivators with each of the Notch receptors to transactivate a Notch target HES1 promoter construct, MAML3 functioned more efficiently with ICN4 than with other forms of ICN. Similarly, MAML1 and MAML2 amplified Notch ligand (both Jagged2 and Delta1)-induced transcription of the HES-1 gene, whereas MAML3 displayed little effect. Thus, MAML proteins may modify Notch signaling in different cell types based on their own expression levels and differential activities and thereby contribute to the diversity of the biological effects resulting from Notch activation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors

Molecular and Cellular Biology , Volume 22 (21): 7688 – Nov 1, 2002

Abstract

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors Lizi Wu 1 , 2 , Tao Sun 2 , 3 , Karla Kobayashi 1 , 2 , Ping Gao 1 , 2 and James D. Griffin 1 , 2 , * 1 Departments of Medical Oncology 3 Pediatric Oncology, Dana-Farber Cancer Institute 2 Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 ABSTRACT The molecular mechanisms by which Notch receptors induce diverse biological responses are not fully understood. We recently cloned a mammalian homologue of the Mastermind gene of Drosophila melanogaster , MAML1 (Mastermind-like-1 molecule) and determined that it functions as a transcriptional coactivator for Notch receptors. In this report, we characterize two additional genes in this Mastermind-like gene family: MAML2 and MAML3. The three MAML genes are widely expressed in adult tissues but exhibit distinct expression patterns in mouse early spinal cord development. All MAML proteins localize to nuclear bodies, share a conserved basic domain in their N termini that binds to the ankyrin repeat domain of Notch, and contain a transcriptional activation domain in their C termini. Moreover, as determined by using coimmunoprecipitation assays, each MAML protein was found to be capable of forming a multiprotein complex with the intracellular domain of each Notch receptor (ICN1 to -4) and CSL in vivo. However, MAML3 bound less efficiently to the ankyrin repeat domain of Notch1. Also, in U20S cells, whereas MAML1 and MAML2 functioned efficiently as coactivators with each of the Notch receptors to transactivate a Notch target HES1 promoter construct, MAML3 functioned more efficiently with ICN4 than with other forms of ICN. Similarly, MAML1 and MAML2 amplified Notch ligand (both Jagged2 and Delta1)-induced transcription of the HES-1 gene, whereas MAML3 displayed little effect. Thus, MAML proteins may modify Notch signaling in different cell types based on their own expression levels and differential activities and thereby contribute to the diversity of the biological effects resulting from Notch activation.

Loading next page...
 
/lp/american-society-for-microbiology/identification-of-a-family-of-mastermind-like-transcriptional-QPsLhLwIXD

References (59)

Publisher
American Society For Microbiology
Copyright
Copyright © 2002 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.22.21.7688-7700.2002
Publisher site
See Article on Publisher Site

Abstract

Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors Lizi Wu 1 , 2 , Tao Sun 2 , 3 , Karla Kobayashi 1 , 2 , Ping Gao 1 , 2 and James D. Griffin 1 , 2 , * 1 Departments of Medical Oncology 3 Pediatric Oncology, Dana-Farber Cancer Institute 2 Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 ABSTRACT The molecular mechanisms by which Notch receptors induce diverse biological responses are not fully understood. We recently cloned a mammalian homologue of the Mastermind gene of Drosophila melanogaster , MAML1 (Mastermind-like-1 molecule) and determined that it functions as a transcriptional coactivator for Notch receptors. In this report, we characterize two additional genes in this Mastermind-like gene family: MAML2 and MAML3. The three MAML genes are widely expressed in adult tissues but exhibit distinct expression patterns in mouse early spinal cord development. All MAML proteins localize to nuclear bodies, share a conserved basic domain in their N termini that binds to the ankyrin repeat domain of Notch, and contain a transcriptional activation domain in their C termini. Moreover, as determined by using coimmunoprecipitation assays, each MAML protein was found to be capable of forming a multiprotein complex with the intracellular domain of each Notch receptor (ICN1 to -4) and CSL in vivo. However, MAML3 bound less efficiently to the ankyrin repeat domain of Notch1. Also, in U20S cells, whereas MAML1 and MAML2 functioned efficiently as coactivators with each of the Notch receptors to transactivate a Notch target HES1 promoter construct, MAML3 functioned more efficiently with ICN4 than with other forms of ICN. Similarly, MAML1 and MAML2 amplified Notch ligand (both Jagged2 and Delta1)-induced transcription of the HES-1 gene, whereas MAML3 displayed little effect. Thus, MAML proteins may modify Notch signaling in different cell types based on their own expression levels and differential activities and thereby contribute to the diversity of the biological effects resulting from Notch activation.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Nov 1, 2002

There are no references for this article.