Abstract
Ubiquitin modification of endosomal membrane proteins is a signal for active inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal degradation. However, the endosome represents a dynamic site of protein sorting with a majority of proteins destined for recycling, rather than MVB targeting. Substrate recognition by ubiquitin ligases is therefore highly regulated. We have investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for understanding ligasesubstrate interactions. Rsp5 interacts directly with its substrate Cps1 via a novel interaction mode. Perturbation of this mode of interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results highlight the ability of Rsp5 to interact with substrates via multiple modalities, suggesting additional mechanisms of regulating this interaction and relevant outcomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 32126-32137 |
| Number of pages | 12 |
| Journal | Journal of Biological Chemistry |
| Volume | 284 |
| Issue number | 46 |
| DOIs | |
| State | Published - 2009 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate recognition. / Lee, Jacqueline R R; Oestreich, Andrea J.; Payne, Johanna A.; Gunawan, Mia S.; Norgan, Andrew P.; Katzmann, David J.
In: Journal of Biological Chemistry, Vol. 284, No. 46, 2009, p. 32126-32137.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate recognition
AU - Lee, Jacqueline R R
AU - Oestreich, Andrea J.
AU - Payne, Johanna A.
AU - Gunawan, Mia S.
AU - Norgan, Andrew P.
AU - Katzmann, David J
PY - 2009
Y1 - 2009
N2 - Ubiquitin modification of endosomal membrane proteins is a signal for active inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal degradation. However, the endosome represents a dynamic site of protein sorting with a majority of proteins destined for recycling, rather than MVB targeting. Substrate recognition by ubiquitin ligases is therefore highly regulated. We have investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for understanding ligasesubstrate interactions. Rsp5 interacts directly with its substrate Cps1 via a novel interaction mode. Perturbation of this mode of interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results highlight the ability of Rsp5 to interact with substrates via multiple modalities, suggesting additional mechanisms of regulating this interaction and relevant outcomes.
AB - Ubiquitin modification of endosomal membrane proteins is a signal for active inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal degradation. However, the endosome represents a dynamic site of protein sorting with a majority of proteins destined for recycling, rather than MVB targeting. Substrate recognition by ubiquitin ligases is therefore highly regulated. We have investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for understanding ligasesubstrate interactions. Rsp5 interacts directly with its substrate Cps1 via a novel interaction mode. Perturbation of this mode of interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results highlight the ability of Rsp5 to interact with substrates via multiple modalities, suggesting additional mechanisms of regulating this interaction and relevant outcomes.
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UR - http://www.scopus.com/inward/citedby.url?scp=70450272538&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.048629
DO - 10.1074/jbc.M109.048629
M3 - Article
C2 - 19744925
AN - SCOPUS:70450272538
VL - 284
SP - 32126
EP - 32137
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -