Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 gag polyprotein Journal Article
| Authors: | Martinez, N. W.; Xue, X.; Berro, R. G.; Kreitzer, G.; Resh, M. D. |
| Article Title: | Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 gag polyprotein |
| Abstract: | Retroviral Gag proteins are synthesized as soluble, myristoylated precursors that traffic to the plasma membrane and promote viral particle production. The intracellular transport of human immunodeficiency virus type 1 (HIV-1) Gag to the plasma membrane remains poorly understood, and cellular motor proteins responsible for Gag movement are not known. Here we show that disrupting the function of KIF4, a kinesin family member, slowed temporal progression of Gag through its trafficking intermediates and inhibited virus-like particle production. Knockdown of KIF4 also led to increased Gag degradation, resulting in reduced intracellular Gag protein levels; this phenotype was rescued by reintroduction of KIF4. When KIF4 function was blocked, Gag transiently accumulated in discrete, perinuclear, nonendocytic clusters that colocalized with endogenous KIF4, with Ubc9, an E2 SUMO-1 conjugating enzyme, and with SUMO. These studies identify a novel transit station through which Gag traffics en route to particle assembly and highlight the importance of KIF4 in regulating HIV-1 Gag trafficking and stability. Copyright © 2008, American Society for Microbiology. All Rights Reserved. |
| Keywords: | controlled study; unclassified drug; human cell; genetics; nonhuman; protein function; protein localization; animal cell; phenotype; animal; metabolism; animals; protein degradation; small interfering rna; protein stability; rna, small interfering; intracellular transport; cercopithecus aethiops; cos cells; physiology; regulatory mechanism; hybrid protein; recombinant fusion proteins; protein transport; cell strain cos1; cercopithecus; cytoplasm; protein family; cell level; sumo-1 protein; ubiquitin-conjugating enzymes; human immunodeficiency virus 1; kinesin; hiv-1; ubiquitin conjugating enzyme; sumo 1 protein; ubiquitin conjugating enzyme e2; gag protein; virus like agent; gag gene products, human immunodeficiency virus; kif4 protein; protein ubc9; kif4a protein, human; ubiquitin conjugating enzyme ubc9; ubiquitin-conjugating enzyme ubc9 |
| Journal Title: | Journal of Virology |
| Volume: | 82 |
| Issue: | 20 |
| ISSN: | 0022-538X |
| Publisher: | American Society for Microbiology |
| Date Published: | 2008-10-01 |
| Start Page: | 9937 |
| End Page: | 9950 |
| Language: | English |
| DOI: | 10.1128/jvi.00819-08 |
| PUBMED: | 18684836 |
| PROVIDER: | scopus |
| PMCID: | PMC2566262 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: JOVIA" - "Source: Scopus" |
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