Abstract
A family of Mastermind-like (MAML) genes encodes critical transcriptional co-activators for Notch signaling, an evolutionarily conserved pathway with numerous roles in both development and human diseases. Notch receptors are cleaved upon ligand engagement and the intracellular domain of Notch shuttles to the nucleus. MAMLs form a functional DNA-binding complex with the cleaved Notch receptor and the transcription factor CSL, thereby regulating transcriptional events that are specific to the Notch pathway. Here, we review recent studies that have utilized molecular, cellular and physiological model system strategies to reveal the pivotal roles of the MAML proteins in Notch signaling. Unexpectedly, however, emerging evidence implicate MAML proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (MEF2C), tumor suppressor pathway (p53) and colon carcinoma survival (β-catenin). Thus, the MAML family appears to function in transcriptional co-activation in a multitude of cellular processes. It is hypothesized that MAML proteins mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alves-Guerra MC, Ronchini C, Capobianco AJ . (2007). Mastermind-like 1 is a specific coactivator of beta-catenin transcription activation and is essential for colon carcinoma cell survival. Cancer Res 67: 8690–8698.
Anderson LM, Gibbons GH . (2007). Notch: a Mastermind of vascular morphogenesis. J Clin Invest 117: 299–302.
Artavanis-Tsakonas S, Rand MD, Lake RJ . (1999). Notch signaling: cell fate control and signal integration in development. Science 284: 770–776.
Aster JC, Pear WS, Blacklow SC . (2008). Notch Signaling in Leukemia. Annu Rev Pathol 3: 587–613.
Bettler D, Pearson S, Yedvobnick B . (1996). The nuclear protein encoded by the Drosophila neurogenic gene Mastermind is widely expressed and associates with specific chromosomal regions. Genetics 143: 859–875.
Bray SJ . (2006). Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7: 678–689.
Brennan K, Gardner P . (2002). Notching up another pathway. Bioessays 24: 405–410.
Fortini ME, Artavanis-Tsakonas S . (1994). The suppressor of hairless protein participates in Notch receptor signaling. Cell 79: 273–282.
Fryer CJ, Lamar E, Turbachova I, Kintner C, Jones KA . (2002). Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev 16: 1397–1411.
Fryer CJ, White JB, Jones KA . (2004). Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16: 509–520.
Go MJ, Artavanis-Tsakonas S . (1998). A genetic screen for novel components of the Notch signaling pathway during Drosophila bristle development. Genetics 150: 211–220.
Hall JM, McDonnell DP . (2005). Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol Interv 5: 343–357.
Han H, Tanigaki K, Yamamoto N, Kuroda K, Yoshimoto M, Nakahata T et al. (2002). Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int Immunol 14: 637–645.
Helms W, Lee H, Ammerman M, Parks AL, Muskavitch MA, Yedvobnick B . (1999). Engineered truncations in the Drosophila Mastermind protein disrupt Notch pathway function. Dev Biol 215: 358–374.
High FA, Zhang M, Proweller A, Tu L, Parmacek MS, Pear WS et al. (2007). An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest 117: 353–363.
Hozumi K, Negishi N, Suzuki D, Abe N, Sotomaru Y, Tamaoki N et al. (2004). Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol 5: 638–644.
Ilagan MX, Kopan R . (2007). SnapShot: Notch signaling pathway. Cell 128: 1246.
Jeffries S, Robbins DJ, Capobianco AJ . (2002). Characterization of a high-molecular-weight Notch complex in the nucleus of Notch(ic)-transformed RKE cells and in a human T-cell leukemia cell line. Mol Cell Biol 22: 3927–3941.
Kankel MW, Hurlbut GD, Upadhyay G, Yajnik V, Yedvobnick B, Artavanis-Tsakonas S . (2007). Investigating the genetic circuitry of Mastermind in Drosophila, a Notch signal effector. Genetics 177: 2493–2505.
Katada T, Kinoshita T . (2003). XMam1, the Xenopus homologue of Mastermind, is essential to primary neurogenesis in Xenopus laevis embryos. Int J Dev Biol 47: 397–404.
Katada T, Ito M, Kojima Y, Miyatani S, Kinoshita T . (2006). XMam1, Xenopus Mastermind1, induces neural gene expression in a Notch-independent manner. Mech Dev 123: 851–859.
Kitagawa M, Oyama T, Kawashima T, Yedvobnick B, Kumar A, Matsuno K et al. (2001). A human protein with sequence similarity to Drosophila Mastermind coordinates the nuclear form of Notch and a CSL protein to build a transcriptional activator complex on target promoters. Mol Cell Biol 21: 4337–4346.
Kopan R, Nye JS, Weintraub H . (1994). The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development 120: 2385–2396.
Kovall RA . (2007). Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex. Curr Opin Struct Biol 17: 117–127.
Lai EC . (2002). Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep 3: 840–845.
Lasky JL, Wu H . (2005). Notch signaling, brain development, and human disease. Pediatr Res 57: 104R–109R.
Li B, Carey M, Workman JL . (2007). The role of chromatin during transcription. Cell 128: 707–719.
Lin SE, Oyama T, Nagase T, Harigaya K, Kitagawa M . (2002). Identification of new human Mastermind proteins defines a family that consists of positive regulators for Notch signaling. J Biol Chem 277: 50612–50620.
Lindsell CE, Shawber CJ, Boulter J, Weinmaster G . (1995). Jagged: a mammalian ligand that activates Notch1. Cell 80: 909–917.
Liu ZJ, Xiao M, Balint K, Smalley KS, Brafford P, Qiu R et al. (2006). Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res 66: 4182–4190.
Luo D, Renault VM, Rando TA . (2005). The regulation of Notch signaling in muscle stem cell activation and postnatal myogenesis. Semin Cell Dev Biol 16: 612–622.
Maillard I, Weng AP, Carpenter AC, Rodriguez CG, Sai H, Xu L et al. (2004). Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 104: 1696–1702.
Nam Y, Sliz P, Song L, Aster JC, Blacklow SC . (2006). Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell 124: 973–983.
Oyama T, Harigaya K, Muradil A, Hozumi K, Habu S, Oguro H et al. (2007). Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo. Proc Natl Acad Sci USA 104: 9764–9769.
Petcherski AG, Kimble J . (2000a). LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 405: 364–368.
Petcherski AG, Kimble J . (2000b). Mastermind is a putative activator for Notch. Curr Biol 10: R471–R473.
Pires-daSilva A, Sommer RJ . (2003). The evolution of signalling pathways in animal development. Nat Rev Genet 4: 39–49.
Proweller A, Tu L, Lepore JJ, Cheng L, Lu MM, Seykora J et al. (2006). Impaired Notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res 66: 7438–7444.
Proweller A, Wright AC, Horng D, Cheng L, Lu MM, Lepore JJ et al. (2007). Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature. Proc Natl Acad Sci USA 104: 16275–16280.
Radtke F, Wilson A, Stark G, Bauer M, van Meerwijk J, MacDonald HR et al. (1999). Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10: 547–558.
Roy M, Pear WS, Aster JC . (2007). The multifaceted role of Notch in cancer. Curr Opin Genet Dev 17: 52–59.
Saint Just Ribeiro M, Hansson ML, Wallberg AE . (2007). A proline repeat domain in the Notch co-activator MAML1 is important for the p300-mediated acetylation of MAML1. Biochem J 404: 289–298.
Saito T, Chiba S, Ichikawa M, Kunisato A, Asai T, Shimizu K et al. (2003). Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity 18: 675–685.
Segditsas S, Tomlinson I . (2006). Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 25: 7531–7537.
Shen H, McElhinny AS, Cao Y, Gao P, Liu J, Bronson R et al. (2006). The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis. Genes Dev 20: 675–688.
Smoller D, Friedel C, Schmid A, Bettler D, Lam L, Yedvobnick B . (1990). The Drosophila neurogenic locus Mastermind encodes a nuclear protein unusually rich in amino acid homopolymers. Genes Dev 4: 1688–1700.
Tanigaki K, Han H, Yamamoto N, Tashiro K, Ikegawa M, Kuroda K et al. (2002). Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nat Immunol 3: 443–450.
Tu L, Fang TC, Artis D, Shestova O, Pross SE, Maillard I et al. (2005). Notch signaling is an important regulator of type 2 immunity. J Exp Med 202: 1037–1042.
Vousden KH, Lane DP . (2007). p53 in health and disease. Nat Rev Mol Cell Biol 8: 275–283.
Wallberg AE, Pedersen K, Lendahl U, Roeder RG . (2002). p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by Notch intracellular domains in vitro. Mol Cell Biol 22: 7812–7819.
Weng AP, Nam Y, Wolfe MS, Pear WS, Griffin JD, Blacklow SC et al. (2003). Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of Notch signaling. Mol Cell Biol 23: 655–664.
Wilson JJ, Kovall RA . (2006). Crystal structure of the CSL–Notch–Mastermind ternary complex bound to DNA. Cell 124: 985–996.
Wu L, Griffin JD . (2004). Modulation of Notch signaling by Mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis. Semin Cancer Biol 14: 348–356.
Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD . (2000). MAML1, a human homologue of Drosophila Mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet 26: 484–489.
Wu L, Kobayashi K, Sun T, Gao P, Liu J, Nakamura M et al. (2004). Cloning and functional characterization of the murine Mastermind-like 1 (Maml1) gene. Gene 328: 153–165.
Wu L, Maillard I, Nakamura M, Pear WS, Griffin JD . (2007). The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development. Blood 110: 3618–3623.
Wu L, Sun T, Kobayashi K, Gao P, Griffin JD . (2002). Identification of a family of Mastermind-like transcriptional coactivators for mammalian Notch receptors. Mol Cell Biol 22: 7688–7700.
Xu T, Artavanis-Tsakonas S . (1990). Deltex, a locus interacting with the neurogenic genes, Notch, Delta and Mastermind in Drosophila melanogaster. Genetics 126: 665–677.
Xu T, Rebay I, Fleming RJ, Scottgale TN, Artavanis-Tsakonas S . (1990). The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. Genes Dev 4: 464–475.
Yedvobnick B, Smoller D, Young P, Mills D . (1988). Molecular analysis of the neurogenic locus Mastermind of Drosophila melanogaster. Genetics 118: 483–497.
Yu S, Reddy JK . (2007). Transcription coactivators for peroxisome proliferator-activated receptors. Biochim Biophys Acta 1771: 936–951.
Zhao Y, Katzman RB, Delmolino LM, Bhat I, Zhang Y, Gurumurthy CB et al. (2007). The Notch regulator MAML1 interacts with p53 and functions as a coactivator. J Biol Chem 282: 11969–11981.
Acknowledgements
This work was supported in part by NIH (R01 CA097148) and Muscular Dystrophy Association (MDA).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
McElhinny, A., Li, JL. & Wu, L. Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways. Oncogene 27, 5138–5147 (2008). https://doi.org/10.1038/onc.2008.228
Published:
Issue Date:
DOI: https://doi.org/10.1038/onc.2008.228
Keywords
This article is cited by
-
Intervening in hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p for tumor microenvironment regulation and cancer therapy
Journal of Nanobiotechnology (2023)
-
A pro B cell population forms the apex of the leukemic hierarchy in Hoxa9/Meis1-dependent AML
Leukemia (2023)
-
Apoptotic proteins with non-apoptotic activity: expression and function in cancer
Apoptosis (2023)
-
Hsa_circ_0007967 promotes gastric cancer proliferation through the miR-411-5p/MAML3 axis
Cell Death Discovery (2022)
-
Temperature sensitivity of Notch signaling underlies species-specific developmental plasticity and robustness in amniote brains
Nature Communications (2022)