How does monoubiquitin turn down Rab5?
Rab5 is monoubiquitinated at specific lysines; ubiquitin at K140/K165 disrupts effector binding and downregulates endocytic trafficking.
Source
Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion
Study at a glance
- Design
- Animal / in-vitro — Mapped Rab5 monoubiquitination sites and tested chemically monoubiquitinated Rab5 function
- N
- Cell-biochemistry of Rab5 ubiquitin sites K116/K140/K165 — no single sample N
- Population
- Cultured cells expressing Rab5 variants
- Outcome
- Site-specific monoubiquitination downregulating Rab5 endocytic signaling
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Inspect source passages
How does monoubiquitin turn down Rab5?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
At which lysines is Rab5 monoubiquitinated?
Here, we demonstrated that Rab5 is monoubiquitinated at K116, K140, and K165 in two different cell lines (HEK 293T and HeLa).
What cellular process does Rab5 regulate?
Rab5 regulates formation of early endosomes and maturation to late endosomes ().
What they did
Mapped Rab5 monoubiquitination sites in cultured cells, built chemically monoubiquitinated Rab5, and tested structure, nucleotide handling, effector binding, and endosome localization.
What they found
Rab5 is monoubiquitinated at K116, K140, and K165; K140/K165 modifications downregulate the Rab5 endocytic pathway via disrupted partners and nucleotide conversion, while K116 has little localization effect.
The limits
What it doesn't show
Does not identify the endogenous E3 ligase or fully map in vivo tissue roles of each site.
Key terms
- Rab5
- Small GTPase controlling early endosome formation/maturation.
- Monoubiquitination
- Attachment of a single ubiquitin to a lysine.
- Effector
- Protein that binds active Rab-GTP to execute trafficking functions.
- GEF/GAP
- Nucleotide exchange and GTPase-activating regulators of Rab cycling.
- Early endosome
- Sorting compartment receiving endocytic cargo.
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Rab5 monoubiquitination sites include:
Common questions
Which lysines are modified?
K116, K140, and K165.
Which sites matter most for downregulation?
K140 and K165; K116 is largely dispensable for localization effects.
What does Rab5 normally do?
Regulates early endosome formation and maturation.
How does ubiquitin impair Rab5?
Disrupts effector interactions and nucleotide conversion.
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