Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus.
LANA2 is a latent protein detected in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected B cells that inhibits p53-dependent transcriptional transactivation and apoptosis and PKR-dependent apoptosis, suggesting an important role in the transforming activity of the virus. It has been reported that LANA2 localizes into the nucleus of both KSHV-infected B cells and transiently transfected HeLa cells. In this study, we show that LANA2 is a nucleocytoplasmic shuttling protein that requires a Rev-type nuclear export signal located in the C-terminus to direct the protein to the cytoplasm, through an association with the export receptor CRM1. In addition, a functional protein kinase B (PKB)/Akt phosphorylation motif partially overlapping with the nuclear export signal was identified. Nuclear exclusion of LANA2 was negatively regulated by the phosphorylation of threonine 564 by Akt. The ability of LANA2 to shuttle between nucleus and cytoplasm has implications for the function of this viral protein.
Muñoz-Fontela
C
C
Departamento de Microbiologia II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal sn, 28040 Madrid, Spain.
Collado
M
M
Rodriguez
E
E
García
M A
MA
Alvarez-Barrientos
A
A
Arroyo
J
J
Nombela
C
C
Rivas
C
C
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D000956:Antigens, Viral / Q000502:physiology*; D019556:COS Cells / Q000821:virology; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D006367:HeLa Cells / Q000821:virology; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism; D017735:Virus Latency / Q000502:physiology; D000097606:Exportin 1 Protein
D000956:Antigens, Viral; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C109540:latency-associated nuclear antigen