Graduate Defense: Jacob Crow
August 12 @ 11:00 am - 1:00 pm MDT
Title: Dimerization of the Notch Intracellular Domain Results in Distinct Signaling Activity
Program: Doctor of Philosophy in Biomolecular Sciences
Advisor: Dr. Allan Albig, Biological Sciences
Committee Members: Dr. Julia Oxford, Biological Sciences, Dr. Kenneth Cornell, Chemistry and Biochemistry, and Dr. Richard Beard, Biological Sciences
The Notch signaling pathway is a core component of metazoan multicellularity; enabling cells to directly communicate with both their neighbors and surrounding microenvironment. These signals are translated directly through the Notch proteins, where a fragment of Notch transitions into the nucleus to act as a co-transcription factor. Commonly involved in pathways that define a cell’s identity and fate, this function requires a signaling system that exists in a state of high-tunability and strict control. One such mechanism is Notch’s ability to homodimerize through specific DNA motifs while within its transcriptional activation complex, resulting in an enhanced transcriptional signal of a select pool of Notch target genes. Of the four mammalian Notch proteins, only the dimerization and sequence motif preferences of Notch1 have been detailed, leaving the capabilities of the other Notch family members unexplored. Despite the Notch proteins’ compositional and structural differences, we found that all Notch proteins are capable of dimerizing with one another, forming both homo- and heterodimers, though with varying frequencies and relative strengths. Further, all Notch homodimers utilized the same selective sequence motif and could not tolerate much deviation from the original mold set by Notch1. Altogether, our results expand the functional interactions and narrow the regulatory outcomes of NICD dimerization, highlighting its distinct role in the Notch signaling pathway.