Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway.

Abstract:

:Numb proteins are evolutionarily conserved signaling molecules that make the daughter cells different after asymmetric divisions by segregating to only one daughter. They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ubiquitin ligases, which target proteins for proteasome-mediated degradation. In Drosophila melanogaster, Numb acts by inhibiting Notch activity to cause a bias in Notch-mediated cell-cell communication. These findings have led to the hypothesis that Numb modulates Notch signaling by using endocytosis and proteasomes to directly reduce Notch protein levels at the cell surface. Here we show that two Drosophila EH proteins, Eps15 homologue 1 (EH1) and the dynamin-associated 160-kDa protein (Dap160), negatively regulate Notch signaling. However, neither elimination of the binding motifs for endocytic proteins nor simultaneous reduction of proteasome activity affects the activity of Numb proteins. Our findings indicate that an endocytosis- and proteasome-independent pathway may mediate Numb signaling in asymmetric cell fate specification.

journal_name

Mol Cell Biol

authors

Tang H,Rompani SB,Atkins JB,Zhou Y,Osterwalder T,Zhong W

doi

10.1128/MCB.25.8.2899-2909.2005

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

2899-909

issue

8

eissn

0270-7306

issn

1098-5549

pii

25/8/2899

journal_volume

25

pub_type

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