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ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function
L Bruhn1, A Munnerlyn, R Grosschedl
1Department of Microbiology, University of California, San Francisco 94143-0414, USA.
Genes & Development
|March 1, 1997
Summary
A novel protein, ALY, interacts with LEF-1 and AML-1 to regulate the T-cell receptor alpha enhancer. ALY is crucial for context-dependent transcriptional activation, facilitating protein collaboration within the enhancer complex.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcription Factors
Background:
- LEF-1 is a transcription factor crucial for T-cell receptor alpha (TCR alpha) enhancer regulation.
- LEF-1's function depends on its HMG domain for DNA bending and an activation domain requiring specific protein contexts.
Purpose of the Study:
- To investigate the function of context-dependent activation domains by identifying novel interacting proteins.
- To clone and characterize ALY, a protein interacting with LEF-1.
Main Methods:
- Cloning of the novel protein ALY.
- Assessing ALY's interaction with LEF-1 and AML-1 activation domains.
- Evaluating ALY's effect on TCR alpha enhancer activity in HeLa and T cells using overexpression and antisense oligonucleotides.
Main Results:
- ALY is a ubiquitously expressed nuclear protein associating with LEF-1 and AML-1 activation domains.
- ALY enhances DNA binding of LEF-1 and AML-1.
- Overexpression of ALY stimulates TCR alpha enhancer activity, while its down-regulation eliminates it.
Conclusions:
- ALY is a key mediator of context-dependent transcriptional activation at the TCR alpha enhancer.
- ALY facilitates functional collaboration among multiple proteins within the TCR alpha enhancer complex.
- ALY's activity is context-specific, similar to LEF-1.