PMID- 23135726
OWN - NLM
STAT- MEDLINE
DCOM- 20130225
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 87
IP  - 2
DP  - 2013 Jan
TI  - Nucleolar trafficking of the mouse mammary tumor virus gag protein induced by 
      interaction with ribosomal protein L9.
PG  - 1069-82
LID - 10.1128/JVI.02463-12 [doi]
AB  - The mouse mammary tumor virus (MMTV) Gag protein directs the assembly in the 
      cytoplasm of immature viral capsids, which subsequently bud from the plasma 
      membranes of infected cells. MMTV Gag localizes to discrete cytoplasmic foci in 
      mouse mammary epithelial cells, consistent with the formation of cytosolic 
      capsids. Unexpectedly, we also observed an accumulation of Gag in the nucleoli of 
      infected cells derived from mammary gland tumors. To detect Gag-interacting 
      proteins that might influence its subcellular localization, a yeast two-hybrid 
      screen was performed. Ribosomal protein L9 (RPL9 or L9), an essential component 
      of the large ribosomal subunit and a putative tumor suppressor, was identified as 
      a Gag binding partner. Overexpression of L9 in cells expressing the MMTV(C3H) 
      provirus resulted in specific, robust accumulation of Gag in nucleoli. Forster 
      resonance energy transfer (FRET) and coimmunoprecipitation analyses demonstrated 
      that Gag and L9 interact within the nucleolus, and the CA domain was the major 
      site of interaction. In addition, the isolated NC domain of Gag localized to the 
      nucleolus, suggesting that it contains a nucleolar localization signal (NoLS). To 
      determine whether L9 plays a role in virus assembly, small interfering RNA 
      (siRNA)-mediated knockdown was performed. Although Gag expression was not reduced 
      with L9 knockdown, virus production was significantly impaired. Thus, our data 
      support the hypothesis that efficient MMTV particle assembly is dependent upon 
      the interaction of Gag and L9 in the nucleoli of infected cells.
FAU - Beyer, Andrea R
AU  - Beyer AR
AD  - Departments of Microbiology and Immunology, Pennsylvania State University College 
      of Medicine, Hershey, PA, USA.
FAU - Bann, Darrin V
AU  - Bann DV
FAU - Rice, Breanna
AU  - Rice B
FAU - Pultz, Ingrid S
AU  - Pultz IS
FAU - Kane, Melissa
AU  - Kane M
FAU - Goff, Stephen P
AU  - Goff SP
FAU - Golovkina, Tatyana V
AU  - Golovkina TV
FAU - Parent, Leslie J
AU  - Parent LJ
LA  - eng
GR  - R01 CA030488/CA/NCI NIH HHS/United States
GR  - F30 CA165774/CA/NCI NIH HHS/United States
GR  - R01 CA76534/CA/NCI NIH HHS/United States
GR  - R01 CA113784/CA/NCI NIH HHS/United States
GR  - T32 GM007183/GM/NIGMS NIH HHS/United States
GR  - R01 CA30488/CA/NCI NIH HHS/United States
GR  - R01 CA076534/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121107
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Gene Products, gag)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (ribosomal protein L9)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleolus/*metabolism
MH  - Epithelial Cells/virology
MH  - Fluorescence Resonance Energy Transfer
MH  - Gene Products, gag/*metabolism
MH  - *Host-Pathogen Interactions
MH  - Immunoprecipitation
MH  - Mammary Tumor Virus, Mouse/*physiology
MH  - Mice
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Interaction Mapping
MH  - Protein Sorting Signals
MH  - Protein Transport
MH  - Ribosomal Proteins/*metabolism
MH  - Two-Hybrid System Techniques
MH  - *Virus Assembly
PMC - PMC3554096
EDAT- 2012/11/09 06:00
MHDA- 2013/02/26 06:00
PMCR- 2013/07/01
CRDT- 2012/11/09 06:00
PHST- 2012/11/09 06:00 [entrez]
PHST- 2012/11/09 06:00 [pubmed]
PHST- 2013/02/26 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - JVI.02463-12 [pii]
AID - 02463-12 [pii]
AID - 10.1128/JVI.02463-12 [doi]
PST - ppublish
SO  - J Virol. 2013 Jan;87(2):1069-82. doi: 10.1128/JVI.02463-12. Epub 2012 Nov 7.