Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA

FEBS Lett. 2006 Jan 9;580(1):93-8. doi: 10.1016/j.febslet.2005.11.057. Epub 2005 Dec 6.

Abstract

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) is known to modulate viral and cellular gene expression. We show that LANA directly associates with an interleukin-6 signal transducer, signal transducer and activator of transcription 3 (STAT3) and that LANA enhances the transcriptional activity of STAT3. Coimmunoprecipitation studies documented a physical interaction between LANA and STAT3 in transiently transfected 293T cells as well as the KSHV-infected primary effusion lymphoma (PEL) cell line. Furthermore, small-interfering RNA-mediated reduction of LANA expression decreased the STAT3-dependent transcription in KSHV-positive PEL cells, whereas overexpression of LANA enhanced STAT3 activity in KSHV-negative B lymphoma cells. These data demonstrate that LANA is a transcriptional co-activator of STAT3, and may have implications for the pathogenesis of KSHV-associated diseases.

MeSH terms

  • Antigens, Viral / genetics
  • Antigens, Viral / metabolism*
  • Cell Line, Tumor
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / metabolism*
  • Herpesvirus 8, Human / pathogenicity
  • Humans
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / virology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / genetics
  • Sarcoma, Kaposi / genetics
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / virology
  • Transcription, Genetic*

Substances

  • Antigens, Viral
  • Nuclear Proteins
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • latency-associated nuclear antigen