Wu GY et al. (1998) Proc Natl Acad Sci U S A "Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin."

Kitajewski JK, Wu GY, Greenwald IS, Hubbard EJA

[Proc Natl Acad Sci U S A, 1998]

Mutations in either of two human presenilin genes (PS1 and PS2) cause Alzheimer's disease. Here we describe genetic and physical interactions between Caenorhabditis elegans SEL-10, a member of the Cdc4p family of proteins, and SEL-12, a C. elegans presenilin. We show that loss of sel-10 activity can suppress the egg-laying defective phenotype associated with reducing sel-12 activity, and that SEL-10 can physically complex with SEL-12. Proteins of the Cdc4p family have been shown to target proteins for ubiquitin-mediated turnover. The functional and physical interaction between sel-10 and sel-12 therefore offers an approach to understanding how presenilin levels are normally regulated.

Hubbard EJA et al. (1997) Genes Dev "sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins."

Hubbard EJA, Greenwald IS, Kitajewski JK, Wu GY

[Genes Dev, 1997]

Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins and has a potential human ortholog. Coimmunoprecipitation data indicate that C. elegans SEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis.