Polyamines are often associated with ribosomes and are thought to stabilize their integrity. In Arabidopsis, the polyamine thermospermine (tSpm) affects xylem cell fate. tSpm induces translation of SU...

Apusomonads are sediment-dwelling bacterivorous protists that are sister to all Opisthokonta. They have been found to show a negative phototactic r...

Small molecules toggling the ubiquitin-proteasome system (UPS) are powerful regulators of protein degradation. Yet, mechanistic knowledge of how endogenous ligands gate UPS decisions remains rudimentary. Here, we define control of UPS access to Tryptophan-2,3-dioxygenase (TDO2), which converts the essential amino acid tryptophan (Trp) to N-formylkynurenine. When Trp concentrations are limiting, TDO2 is degraded to avert tryptophanemia. Using CRISPRi screening and biochemistry, we identify a CK2-FBXW11 kinase-E3 ligase cascade that generates and recognizes tandem TDO2 phosphodegrons when not protected by Trp. Trp binding to an exosite safeguards TDO2 from phosphorylation-dependent ubiquitylation. Effects of Trp analogs on CK2-FBXW11-dependent ubiquitylation indicated that the indole, amino, and carboxylate groups are necessary for substrate shielding. Cryo-EM reveals how these moieties order a region proximal to the phosphodegrons; without Trp, this segment is flexible, enabling phosphorylation-coupled ubiquitylation. Overall, our data uncovered an endogenous small molecule allosterically stabilizing its own metabolizing enzyme through protection from a phosphorylation-ubiquitylation cascade. ### Competing Interest Statement B.A.S. is a member of the scientific advisory boards of Proxygen and Lyterian. The other authors declare no competing interests. Max Planck Society, https://ror.org/01hhn8329 European Union, ERC AdvG, UPSmeetMet, 101098161 to BAS Boehringer Ingelheim Fonds, https://ror.org/00dkye506

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How plant viruses are restricted to the phloem are long-standing questions in plant virology. The paper shows PENETRATION3 activity and callose deposition confine plant viruses to the phloem, which fa...

Plants rely on rapid proteome remodeling to withstand fluctuating environmental conditions, yet how the ubiquitin system dynamically coordinates these multilayered responses remains unclear. Here we d...

Background Plant growth depends on the integration of environmental signals and nutrient availability. Under stress conditions, growth is often attenuated to prioritise defense, creating a trade-off b...