Conserved signal peptide of Notch3 inhibits interaction with proteasome.

Abstract:

:The Notch3 N-terminal sequence is conserved across several mammalian species but diverges from the three other Notch proteins. We determined the significance of the N-terminal sequence using deletion mutants. The first 39 amino acids are required for Notch3 receptor expression, processing, and functional activity. In contrast, the first 14 amino acids do not appear to enhance function, yet are required to reduce ectopic cytoplasmic expression of Notch3. We screened binding partners for cytoplasmic expressed Notch3 using a yeast two-hybrid assay. Notch3 binds specifically to the proteasome subunit PSMA1, and increased cytoplasmic expression of Notch3 results in inhibition of proteasome activity. Our findings support a multifunctional role for the conserved N-terminal sequence of Notch3: targeting of the protein to the secretory pathway and reduction of cytoplasmic Notch3 expression which may inhibit cytoplasmic functions.

authors

Zhang Y,Jia L,Lee SJ,Wang MM

doi

10.1016/j.bbrc.2007.01.151

subject

Has Abstract

pub_date

2007-03-30 00:00:00

pages

245-51

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)00208-2

journal_volume

355

pub_type

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