Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing.

By T. Hoppe, K. Matuschewski, M. Rapé, S. Schlenker, H. Ulrich, S. Jentsch. Cell, 2000

598 citations recorded by the source corpus.

Processing of integral membrane proteins in order to liberate active proteins is of exquisite cellular importance. Examples are the processing events that govern sterol regulation, Notch signaling, the unfolded protein response, and APP fragmentation linked to Alzheimer's disease. In these cases, the proteins are thought to be processed by regulated intramembrane proteolysis, involving site-specific, membrane-localized proteases. Here we show that two homologous yeast transcription factors SPT23 and MGA2 are made as dormant ER/nuclear membrane-localized precursors and become activated by a completely different mechanism that involves ubiquitin/proteasome-dependent processing. SPT23 and MGA2 are relatives of mammalian NF-kappaB and control unsaturated fatty acid levels. Intriguingly, proteasome-dependent processing of SPT23 is regulated by fatty acid pools, suggesting that the precursor itself or interacting partners are sensors of membrane composition or fluidity.

Subfields: Cell Biology, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fc2258df7f1eaa42978e2ccb1455d814910526f6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Aaron Ciechanover
2. M. Glickman
3. M. Rapé
4. D. Komander
5. A. Goldberg

In Genetics

1. D. Komander

In Molecular Biology

1. Aaron Ciechanover
2. D. Komander
3. J. Vance
4. M. Rapé
5. D. Vance
6. M. Glickman
7. A. Goldberg

Citations in the corpus

• The ubiquitin code. (2012, background): “…several C-terminal lysine residues, and in-frame fusions of ubiquitin to p53 are www.annualreviews.org • The Ubiquitin Code 219 by export signal in p53, monoubiquitylation likely changes the in p53 to the export machinery, rather than being an export sufficient to drive its nuclear export (5).”
• The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. (2002, background): “After ubiquitination and proteolysis by the proteasome, the active p90 NH2-terminal region of Spt23 is liberated from the inactive membrane-bound intact p120 form (181).”
• Fatty acid desaturation and chain elongation in eukaryotes (2003, background): “The N-terminal SPT23 transcription factor moves to the nucleus and shuts off transcription of the OLEI gene [27,28].”