scholarly journals An Internal Signal Sequence Mediates the Targeting and Retention of the Human UDP-Glucuronosyltransferase 1A6 to the Endoplasmic Reticulum

1999 ◽  
Vol 274 (44) ◽  
pp. 31401-31409 ◽  
Author(s):  
Mohamed Ouzzine ◽  
Jacques Magdalou ◽  
Brian Burchell ◽  
Sylvie Fournel-Gigleux
Keyword(s):  
Endoplasmic Reticulum ◽  
Signal Sequence ◽  
Internal Signal ◽  
Udp Glucuronosyltransferase

scholarly journals C-terminal sequences can inhibit the insertion of membrane proteins into the endoplasmic reticulum of Saccharomyces cerevisiae.

1992 ◽  
Vol 12 (1) ◽  
pp. 276-282 ◽  
Author(s):  
N Green ◽  
P Walter
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Fusion Proteins ◽  
Signal Sequence ◽  
Dna Encoding ◽  
Luminal Side ◽  
Internal Signal ◽  
Histidinol Dehydrogenase ◽  
Arginine Permease ◽  
Er Membrane

We have constructed three gene fusions that encode portions of a membrane protein, arginine permease, fused to a reporter domain, the cytoplasmic enzyme histidinol dehydrogenase (HD), located at the C-terminal end. These fusion proteins contain at least one of the internal signal sequences of arginine permease. When the fusion proteins were expressed in Saccharomyces cerevisiae and inserted into the endoplasmic reticulum (ER), two of the fusion proteins placed HD on the luminal side of the ER membrane, but only when a piece of DNA encoding a spacer protein segment was inserted into the fusion joint. The third fusion protein, with or without the spacer included, placed HD on the cytoplasmic side of the membrane. These results suggest that (i) sequences C-terminal to the internal signal sequence can inhibit membrane insertion and (ii) HD requires a preceding spacer segment to be translocated across the ER membrane.

C-terminal sequences can inhibit the insertion of membrane proteins into the endoplasmic reticulum of Saccharomyces cerevisiae

1992 ◽  
Vol 12 (1) ◽  
pp. 276-282
Author(s):  
N Green ◽  
P Walter
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Fusion Proteins ◽  
Signal Sequence ◽  
Dna Encoding ◽  
Luminal Side ◽  
Internal Signal ◽  
Histidinol Dehydrogenase ◽  
Arginine Permease ◽  
Er Membrane

We have constructed three gene fusions that encode portions of a membrane protein, arginine permease, fused to a reporter domain, the cytoplasmic enzyme histidinol dehydrogenase (HD), located at the C-terminal end. These fusion proteins contain at least one of the internal signal sequences of arginine permease. When the fusion proteins were expressed in Saccharomyces cerevisiae and inserted into the endoplasmic reticulum (ER), two of the fusion proteins placed HD on the luminal side of the ER membrane, but only when a piece of DNA encoding a spacer protein segment was inserted into the fusion joint. The third fusion protein, with or without the spacer included, placed HD on the cytoplasmic side of the membrane. These results suggest that (i) sequences C-terminal to the internal signal sequence can inhibit membrane insertion and (ii) HD requires a preceding spacer segment to be translocated across the ER membrane.

Efficiency and diversity of protein localization by random signal sequences

1990 ◽  
Vol 10 (6) ◽  
pp. 3163-3173
Author(s):  
C A Kaiser ◽  
D Botstein
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Signal Peptide ◽  
Signal Sequence ◽  
Protein Localization ◽  
Random Signal ◽  
Perinuclear Region ◽  
Hybrid Protein ◽  
Random Sequences ◽  
Beta Galactosidase

Three randomly derived sequences that can substitute for the signal peptide of Saccharomyces cerevisiae invertase were tested for the efficiency with which they can translocate invertase or beta-galactosidase into the endoplasmic reticulum. The rate of translocation, as measured by glycosylation, was estimated in pulse-chase experiments to be less than 6 min. When fused to beta-galactosidase, these peptides, like the normal invertase signal sequence, direct the hybrid protein to a perinuclear region, consistent with localization to the endoplasmic reticulum. The diversity of function of random peptides was studied further by immunofluorescence localization of proteins fused to 28 random sequences: 4 directed the hybrid to the endoplasmic reticulum, 3 directed it to the mitochondria, and 1 directed it to the nucleus.

scholarly journals Small Molecule Targets Env for Endoplasmic Reticulum-Associated Protein Degradation and Inhibits Human Immunodeficiency Virus Type 1 Propagation

2009 ◽  
Vol 83 (19) ◽  
pp. 10075-10084 ◽  
Author(s):  
Alenka Jejcic ◽  
Robert Daniels ◽  
Laura Goobar-Larsson ◽  
Daniel N. Hebert ◽  
Anders Vahlne
Keyword(s):  
Human Immunodeficiency Virus ◽  
Endoplasmic Reticulum ◽  
Protein Degradation ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Signal Sequence ◽  
Immunodeficiency Virus ◽  
Steady State Levels ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) is dependent on its envelope glycoprotein (Env) to bind, fuse, and subsequently infect a cell. We show here that treatment of HIV-1-infected cells with glycyl-prolyl-glycine amide (GPG-NH2), dramatically reduced the infectivity of the released viral particles by decreasing their Env incorporation. The mechanism of GPG-NH2 was uncovered by examining Env expression and maturation in treated cells. GPG-NH2 treatment was found to affect Env by significantly decreasing its steady-state levels, its processing into gp120/gp41, and its mass by inducing glycan removal in a manner dependent on its native signal sequence and the proteasome. Therefore, GPG-NH2 negatively impacts Env maturation, facilitating its targeting for endoplasmic reticulum-associated protein degradation, where Env is deglycosylated en route to its degradation. These findings illustrate that nontoxic drugs such as GPG-NH2, which can selectively target glycoproteins to existing cellular degradation pathways, may be useful for pathogen therapy.

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