Abstract
Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through direct cell-to-cell interactions. Inappropriate release of the intracellular domain of Notch (NICD) from the plasma membrane results in the accumulation of deregulated nuclear NICD that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear NICD forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression. Although it is well understood that NICD forms a transcriptional activation complex, little is known about how the complex is assembled. In this study, we demonstrate that NICD multimerizes and that these multimers function as precursors for the stepwise assembly of the Notch activation complex. Importantly, we demonstrate that the assembly is mediated by NICD multimers interacting with Skip and Mastermind. These interactions form a preactivation complex that is then resolved by CSL to form the Notch transcriptional activation complex on DNA.
| Original language | English |
|---|---|
| Pages (from-to) | 1396-1408 |
| Number of pages | 13 |
| Journal | Molecular and Cellular Biology |
| Volume | 31 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 1 2011 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Assembly of a notch transcriptional activation complex requires multimerization. / Vasquez-Del Carpio, Rodrigo; Kaplan, Fred M.; Weaver, Kelly L.; VanWye, Jeffrey D.; Alves-Guerra, Marie Clotilde; Robbins, David J; Capobianco, Anthony J.
In: Molecular and Cellular Biology, Vol. 31, No. 7, 01.04.2011, p. 1396-1408.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Assembly of a notch transcriptional activation complex requires multimerization
AU - Vasquez-Del Carpio, Rodrigo
AU - Kaplan, Fred M.
AU - Weaver, Kelly L.
AU - VanWye, Jeffrey D.
AU - Alves-Guerra, Marie Clotilde
AU - Robbins, David J
AU - Capobianco, Anthony J
PY - 2011/4/1
Y1 - 2011/4/1
N2 - Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through direct cell-to-cell interactions. Inappropriate release of the intracellular domain of Notch (NICD) from the plasma membrane results in the accumulation of deregulated nuclear NICD that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear NICD forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression. Although it is well understood that NICD forms a transcriptional activation complex, little is known about how the complex is assembled. In this study, we demonstrate that NICD multimerizes and that these multimers function as precursors for the stepwise assembly of the Notch activation complex. Importantly, we demonstrate that the assembly is mediated by NICD multimers interacting with Skip and Mastermind. These interactions form a preactivation complex that is then resolved by CSL to form the Notch transcriptional activation complex on DNA.
AB - Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through direct cell-to-cell interactions. Inappropriate release of the intracellular domain of Notch (NICD) from the plasma membrane results in the accumulation of deregulated nuclear NICD that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear NICD forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression. Although it is well understood that NICD forms a transcriptional activation complex, little is known about how the complex is assembled. In this study, we demonstrate that NICD multimerizes and that these multimers function as precursors for the stepwise assembly of the Notch activation complex. Importantly, we demonstrate that the assembly is mediated by NICD multimers interacting with Skip and Mastermind. These interactions form a preactivation complex that is then resolved by CSL to form the Notch transcriptional activation complex on DNA.
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U2 - 10.1128/MCB.00360-10
DO - 10.1128/MCB.00360-10
M3 - Article
VL - 31
SP - 1396
EP - 1408
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 7
ER -