ArticleProceedings of the National Academy of Sciences of the United States of America2010
Retroviral Rem protein requires processing by signal peptidase and retrotranslocation for nuclear function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed.
- A Viral Protein Antagonist for Both AID and APOBEC3.Viruses · 2026Review
- Characterization of HERV-K (HML-2) Rec proteins encoded in the human genome and their post-transcriptional function.Journal of virology · 2025Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Apobec-mediated retroviral hypermutation in vivo is dependent on mouse strain.PLoS pathogens · 2024Article
- The Feline Immunodeficiency Virus Envelope Signal Peptide Is a Tetherin Antagonizing Protein.mBio · 2023Article
- Life after Cleavage: The Story of a β-Retroviral (MMTV) Signal Peptide-From Murine Lymphoma to Human Breast Cancer.Viruses · 2022Review
- The Bombyx mori Nucleopolyhedrovirus GP64 Retains the Transmembrane Helix of Signal Peptide to Contribute to Secretion across the Cytomembrane.Microbiology spectrum · 2022Article
- Article
- How Viruses Use the VCP/p97 ATPase Molecular Machine.Viruses · 2021Review
- Unconventional p97/VCP-Mediated Endoplasmic Reticulum-to-Endosome Trafficking of a Retroviral Protein.Journal of virology · 2021Article
- Review
- A Protein Antagonist of Activation-Induced Cytidine Deaminase Encoded by a Complex Mouse Retrovirus.mBio · 2019Article
- Article
- Article
- Review
- Opportunistic intruders: how viruses orchestrate ER functions to infect cells.Nature reviews. Microbiology · 2016Review
- Competitive Inhibition of the Endoplasmic Reticulum Signal Peptidase by Non-cleavable Mutant Preprotein Cargos.The Journal of biological chemistry · 2015Article
- Role for a Zinc Finger Protein (Zfp111) in Transformation of 208F Rat Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Protein.Journal of virology · 2015Article
- APOBECs and virus restriction.Virology · 2015Review
- Retroviral vectors elevate coexpressed protein levels in trans through cap-dependent translation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Mouse mammary tumor virus (MMTV) is a complex murine retrovirus that encodes an HIV Rev-like export protein, Rem, from a doubly spliced version of envelope (Env) mRNA. Previously, the N-terminal 98-amino acid sequence of Rem, which is identical to Env signal peptide (SP), and full-length Rem were shown to be functional in a reporter assay that measures a postexport function. Here we show that MMTV-infected cells or cells transfected with rem or env cDNAs express SP, which is the active component in the reporter assay. Uncleaved Rem was partially glycosylated, but mutations in both glycosylation sites within the C terminus prevented Rem function. Mutations that reduced Rem or Env cleavage by signal peptidase greatly reduced SP levels and functional activity in the reporter assay and allowed accumulation of the uncleaved protein. Fluorescence microscopy revealed that GFP-tagged cleavage-site mutants are unstable and lack fluorescence compared with wild-type Rem, suggesting improper folding. Proteasome inhibitors allowed accumulation of uncleaved Rem relative to SP and increased reporter activity, consistent with SP retrotranslocation and proteasome escape before nuclear entry. Expression of a dominant-negative p97 ATPase did not alter levels of unprocessed Rem and SP but decreased reporter activity, suggesting p97-facilitated retrotranslocation of SP. Our results provide an example of a SP that is processed by signal peptidase and retrotranslocated to allow nuclear localization and function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.