INVESTIGADORES
VALDEZ Javier Esteban
artículos
Título:
?Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins?
Autor/es:
HETTEMA EH; VALDEZ TAUBAS J; PELHAM HR
Revista:
EMBO JOURNAL
Referencias:
Año: 2004 vol. 23 p. 1279 - 1288
ISSN:
0261-4189
Resumen:
Membrane proteins destined for the vacuolar or lysosomal
lumen are typically ubiquitinated, the ubiquitin serving as
a targeting signal for the multivesicular body pathway.
The RING-domain ubiquitin ligase Tul1 is an integral
membrane protein that modifies the yeast vacuolar enzyme
carboxypeptidase S (Cps1), the polyphosphatase
Ppn1/Phm5 and other proteins containing exposed hydrophilic
residues within their transmembrane domains
(TMDs). Here we show that Bsd2 provides an alternative
ubiquitination mechanism for Cps1, Phm5 and other proteins.
Bsd2 is a three-TMD protein with a PPXY motif that
binds the HECT domain ubiquitin ligase Rsp5. It can thus
act as a specific adaptor linking Rsp5 to its substrates. Like
Tul1, the Bsd2 system recognises polar TMDs. Bsd2 also
controls the vacuolar targeting of a manganese transporter
and a mutant plasma membrane ATPase, and together
with the ER retrieval receptor Rer1, it protects cells from
stress. We suggest that Bsd2 has a wide role in the quality
control of membrane proteins. Bsd2 is the yeast homologue
of human NEDD4 binding protein N4WBP5, which
may therefore have similar functions.