# Drosophila Smad2 degradation occurs independently of linker phosphorylations

## TL;DR

This study shows that the degradation of a key signaling protein in fruit flies happens without specific phosphorylation events and not through the usual cellular cleanup system.

## Contribution

The paper reveals that dSmad2 degradation does not depend on linker phosphorylations or proteasomes, challenging current understanding of TGF-β signaling regulation.

## Key findings

- dSmad2 degradation occurs without phosphorylation at linker sites 252 and 277.
- Proteasomes are not responsible for the degradation of activated dSmad2.
- Phosphorylation at the C-terminus is still necessary for dSmad2 activation.

## Abstract

TGF-β signals are important for proliferation, differentiation, and cell fate determination during embryonic development and tissue homeostasis in adults.
Drosophila
Activin/TGF-β signals are transduced intracellularly when its transcription factor dSmad2 (also called Smad on X or Smox) is C-terminally phosphorylated by pathway receptors. Recently, it has been shown that receptor-activated dSmad2 undergoes bulk degradation, however, the mechanism of how this occurs is unknown. Here we investigated if two putative linker phosphorylation sites are involved in dSmad2 degradation. We demonstrate that degradation of activated-dSmad2 occurs independently of threonine phosphorylation at linker sites 252 and 277. We also show that dSmad2 degradation is not carried out by cellular proteasomes.