Assembly of a notch transcriptional activation complex requires multimerization

Rodrigo Vasquez-Del Carpio, Fred M. Kaplan, Kelly L. Weaver, Jeffrey D. VanWye, Marie Clotilde Alves-Guerra, David J Robbins, Anthony J Capobianco

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)1396-1408
Number of pages13
JournalMolecular and Cellular Biology
Volume31
Issue number7
DOIs
StatePublished - Apr 1 2011

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Transcriptional Activation
Notch Receptors
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
DNA-Binding Proteins
Cell Communication
Cell Membrane
Gene Expression
DNA
Neoplasms
Proteins

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 journalArticle

Vasquez-Del Carpio, R, Kaplan, FM, Weaver, KL, VanWye, JD, Alves-Guerra, MC, Robbins, DJ & Capobianco, AJ 2011, 'Assembly of a notch transcriptional activation complex requires multimerization', Molecular and Cellular Biology, vol. 31, no. 7, pp. 1396-1408. https://doi.org/10.1128/MCB.00360-10
Vasquez-Del Carpio R, Kaplan FM, Weaver KL, VanWye JD, Alves-Guerra MC, Robbins DJ et al. Assembly of a notch transcriptional activation complex requires multimerization. Molecular and Cellular Biology. 2011 Apr 1;31(7):1396-1408. https://doi.org/10.1128/MCB.00360-10
Vasquez-Del Carpio, Rodrigo ; Kaplan, Fred M. ; Weaver, Kelly L. ; VanWye, Jeffrey D. ; Alves-Guerra, Marie Clotilde ; Robbins, David J ; Capobianco, Anthony J. / Assembly of a notch transcriptional activation complex requires multimerization. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 7. pp. 1396-1408.
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