Characterization of sel-8 and sel-12, two genes that interact with lin-12.

다국어 초록 (Multilingual Abstract)

LIN-12 and GLP-1 are members of the LIN-12/Notch family of receptors that mediate cell-cell interactions during development. The <italic>sel-8 </italic> and <italic>sel-12</italic> genes were both isolated in screens for suppressors of mutations that constitutively activate LIN-12. I describe the cloning and characterization of <italic>sel-8</italic> and perform functional studies on <italic>sel-12</italic>.
Here, I extend the genetic characterization of <italic>sel-8</italic> and clone it, showing that SEL-8 is a novel, highly glutamine-rich, nuclear protein. I also show that <italic>sel-8</italic> is essential for signaling mediated by <italic>lin-12</italic> and <italic>glp-1</italic>. Models are discussed involving the potential role of SEL-8 as a transcriptional coactivator or assembly factor for a transcription complex containing the intracellular domains of LIN-12 or GLP-1. The <italic>sel-12</italic> gene encodes a presenilin, a kind of gene that causes Alzheimer's disease when mutated in humans. Here, I examine the effects of transgenically expressing both <italic>sel-12</italic> and human presenilins with missense mutations that cause Alzheimer's disease. Such mutations cause no obvious gain-of-function phenotypes, but human presenilins show partially reduced ability to functionally substitute for <italic>sel-12 </italic>. I then show that a human presenilin that carries mutations associated with colorectal tumors also show reduced activity in a similar assay. Finally, I show that the mutation of a conserved aspartate residue of <italic>sel-12 </italic> causes the gene to behave like an antimorph when transgenically expressed.