Identification of a Novel Bcl10 Domain that Contributes to NK-kappaB Activation
Abstract
The NF-B transcription factor is a centrally important mediator of T cell functional responses. However, much is still unknown of the regulation of this pathway. Activation of the NF-B signaling cascade via numerous cell receptors, including the T cell receptor (TCR), requires the adaptor proteinBcl10. The function of Bcl10 in the NF-B pathway, as well as other pathways, is not yet completely understood. In this work, I investigated the function of a 12-amino acid peptide on the Bcl10 N-terminus, dubbed the N-terminal peptide. As there is currently no crystal structure of the Bcl10 protein, I developed N-terminal peptide mutants, targeting amino acids that are potentially important to the function of the peptide. Through mutation of key amino acids to alanine as well as deletion of groups of amino acids, I determined that the N-terminal peptide functions to positively influence Bcl10 activation of downstream NF-B. This research also supports the function of the N-terminal peptide in Bcl10 binding to partner proteins, including CARMA1 and MALT1, as well as Bcl10 intracellular redistribution, and Bcl10protein stability.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 22, 2012
- Accession Number
- AD1013263
Entities
People
- Ashley C. Shaloo
Organizations
- Uniformed Services University of the Health Sciences