MamL-1 domain

Last updated
MamL-1
Identifiers
SymbolMamL-1
Pfam PF09596
InterPro IPR019082
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In molecular biology, there are a number of neurogenic proteins referred to as mastermind-like proteins (MAMLs) of which this domain is the N-terminal region. Mastermind-like proteins act as critical transcriptional co-activators for Notch signaling. [1] [2]

Domain

The N-terminal domain of MAML proteins, MAML1, MAML2, MAML3, is a polypeptide of up to 70 residues, numbers 15-67 of which adopt an elongated kinked helix that wraps around ANK and CSL [3] [4] forming one of the complexes in the build-up of the Notch transcriptional complex for recruiting general transcription factors. This N-terminal domain is responsible for its interaction with the ankyrin repeat region of the Notch proteins NOTCH1, [5] NOTCH2, [6] NOTCH3 [7] and NOTCH4. It forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1, and also binds CREBBP/CBP [8] and CDK8. [9] The C-terminal region is required for transcriptional activation.

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. MAML proteins may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C), [10] tumour suppressor pathway (p53) [11] and colon carcinoma survival (beta-catenin). [12] MAML proteins could 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.

Related Research Articles

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<span class="mw-page-title-main">Mediator (coactivator)</span>

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<span class="mw-page-title-main">Mef2</span> Protein family

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<span class="mw-page-title-main">Nuclear receptor co-repressor 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">JAG1</span> Protein-coding gene in the species Homo sapiens

Jagged1 (JAG1) is one of five cell surface proteins (ligands) that interact with four receptors in the mammalian Notch signaling pathway. The Notch Signaling Pathway is a highly conserved pathway that functions to establish and regulate cell fate decisions in many organ systems. Once the JAG1-NOTCH (receptor-ligand) interactions take place, a cascade of proteolytic cleavages is triggered resulting in activation of the transcription for downstream target genes. Located on human chromosome 20, the JAG1 gene is expressed in multiple organ systems in the body and causes the autosomal dominant disorder Alagille syndrome (ALGS) resulting from loss of function mutations within the gene. JAG1 has also been designated as CD339.

<span class="mw-page-title-main">Notch 1</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog protein 1(Notch 1) is a protein encoded in humans by the NOTCH1 gene. Notch 1 is a single-pass transmembrane receptor.

<span class="mw-page-title-main">Retinoid X receptor alpha</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Notch 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MED1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">RBPJ</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Cyclin-dependent kinase 8</span> Protein-coding gene in the species Homo sapiens

Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.

<span class="mw-page-title-main">HES1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MED14</span> Protein-coding gene in humans

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<span class="mw-page-title-main">CRTC1</span> Protein-coding gene in the species Homo sapiens

CREB-regulated transcription coactivator 1 (CRTC1), previously referred to as TORC1 (Transducer Of Regulated CREB activity 1), is a protein that in humans is encoded by the CRTC1 gene. It is expressed in a limited number of tissues that include fetal brain and liver and adult heart, skeletal muscles, liver and salivary glands and various regions of the adult central nervous system.

<span class="mw-page-title-main">MED21</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">THRAP3</span> Protein-coding gene in the species Homo sapiens

Thyroid hormone receptor-associated protein 3 is a protein that in humans is encoded by the THRAP3 gene.

<span class="mw-page-title-main">MAML1</span> Protein-coding gene in the species Homo sapiens

Mastermind-like protein 1 is a protein that in humans is encoded by the MAML1 gene.

<span class="mw-page-title-main">MAML2</span> Protein-coding gene in the species Homo sapiens

Mastermind-like protein 2 is a protein that in humans is encoded by the MAML2 gene.

The Epstein–Barr virus nuclear antigen 2 (EBNA-2) is one of the six EBV viral nuclear proteins expressed in latently infected B lymphocytes is a transactivator protein. EBNA2 is involved in the regulation of latent viral transcription and contributes to the immortalization of EBV infected cells. EBNA2 acts as an adapter molecule that binds to cellular sequence-specific DNA-binding proteins, JK recombination signal-binding protein (RBP-JK), and PU.1 as well as working with multiple members of the RNA polymerase II transcription complex.

<span class="mw-page-title-main">Notch proteins</span> Protein family

Notch proteins are a family of type 1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans. The Notch extracellular domain mediates interactions with DSL family ligands, allowing it to participate in juxtacrine signaling. The Notch intracellular domain acts as a transcriptional activator when in complex with CSL family transcription factors. Members of this type 1 transmembrane protein family share several core structures, including an extracellular domain consisting of multiple epidermal growth factor (EGF)-like repeats and an intracellular domain transcriptional activation domain (TAD). Notch family members operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Much of what is known about Notch function comes from studies done in Caenorhabditis elegans (C.elegans) and Drosophila melanogaster. Human homologs have also been identified, but details of Notch function and interactions with its ligands are not well known in this context.

References

  1. McElhinny AS, Li JL, Wu L (September 2008). "Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways". Oncogene. 27 (38): 5138–47. doi: 10.1038/onc.2008.228 . PMID   18758483.
  2. Kovall RA (September 2008). "More complicated than it looks: assembly of Notch pathway transcription complexes". Oncogene. 27 (38): 5099–109. doi:10.1038/onc.2008.223. PMID   18758478.
  3. Schroeter EH, Kisslinger JA, Kopan R (May 1998). "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain". Nature . 393 (6683): 382–6. doi:10.1038/30756. PMID   9620803. S2CID   4431882.
  4. Wilson JJ, Kovall RA (March 2006). "Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA". Cell . 124 (5): 985–96. doi: 10.1016/j.cell.2006.01.035 . PMID   16530045. S2CID   9224353.
  5. Chiang MY, Xu ML, Histen G, Shestova O, Roy M, Nam Y, Blacklow SC, Sacks DB, Pear WS, Aster JC (August 2006). "Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1". Mol. Cell. Biol. 26 (16): 6261–71. doi:10.1128/MCB.02478-05. PMC   1592797 . PMID   16880534.
  6. Wu L, Maillard I, Nakamura M, Pear WS, Griffin JD (November 2007). "The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development". Blood. 110 (10): 3618–23. doi:10.1182/blood-2007-06-097030. PMC   2077311 . PMID   17699740.
  7. Liu H, Kennard S, Lilly B (February 2009). "NOTCH3 expression is induced in mural cells through an autoregulatory loop that requires endothelial-expressed JAGGED1". Circ. Res. 104 (4): 466–75. doi:10.1161/CIRCRESAHA.108.184846. PMC   2747310 . PMID   19150886.
  8. Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, Griffin JD (July 2005). "Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation". EMBO J. 24 (13): 2391–402. doi:10.1038/sj.emboj.7600719. PMC   1173159 . PMID   15961999.
  9. Fryer CJ, White JB, Jones KA (November 2004). "Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover". Mol. Cell. 16 (4): 509–20. doi: 10.1016/j.molcel.2004.10.014 . PMID   15546612.
  10. Shen H, McElhinny AS, Cao Y, Gao P, Liu J, Bronson R, Griffin JD, Wu L (March 2006). "The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis". Genes Dev. 20 (6): 675–88. doi:10.1101/gad.1383706. PMC   1413284 . PMID   16510869.
  11. Zhao Y, Katzman RB, Delmolino LM, Bhat I, Zhang Y, Gurumurthy CB, Germaniuk-Kurowska A, Reddi HV, Solomon A, Zeng MS, Kung A, Ma H, Gao Q, Dimri G, Stanculescu A, Miele L, Wu L, Griffin JD, Wazer DE, Band H, Band V (April 2007). "The notch regulator MAML1 interacts with p53 and functions as a coactivator". J. Biol. Chem. 282 (16): 11969–81. doi: 10.1074/jbc.M608974200 . PMID   17317671.
  12. Alves-Guerra MC, Ronchini C, Capobianco AJ (September 2007). "Mastermind-like 1 Is a specific coactivator of beta-catenin transcription activation and is essential for colon carcinoma cell survival". Cancer Res. 67 (18): 8690–8. doi:10.1158/0008-5472.CAN-07-1720. PMID   17875709.
This article incorporates text from the public domain Pfam and InterPro: IPR019082