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Updated: Jul 11, 2026

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)
07:02

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)

Published on: September 14, 2010

Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by

Ke Lan1, Subhash C Verma, Masanao Murakami

  • 1Department of Microbiology and Tumor Virology Program of Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 3, 2007
PubMed

Insights

Kaposi's sarcoma-associated herpesvirus LANA protein hijacks Sel10, a tumor suppressor, to stabilize intracellular activated Notch (ICN). This promotes the proliferation of virus-infected tumor cells.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • The Notch signaling pathway is crucial for cell regulation but its deregulation is linked to cancer.
  • Intracellular activated Notch (ICN) stability is controlled by the Sel10-mediated ubiquitin-proteasome pathway, with Sel10 acting as a tumor suppressor.
  • Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus implicated in various cancers.

Purpose of the Study:

  • To investigate the interaction between KSHV latency-associated nuclear antigen (LANA) and the Sel10 protein.
  • To elucidate the mechanism by which LANA affects ICN stability and cellular proliferation in KSHV-infected cells.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Western blotting to assess protein levels and ubiquitination.
  • Cell-based assays to evaluate cellular proliferation.

Main Results:

  • KSHV LANA directly interacts with Sel10, forming a complex in infected cells.
  • LANA binding to Sel10 inhibits the ubiquitination and degradation of ICN.
  • The carboxyl terminus of LANA competes with ICN for Sel10 binding, leading to elevated ICN levels.
  • Elevated ICN levels contribute to enhanced proliferation of KSHV-infected tumor cells.

Conclusions:

  • KSHV LANA protein suppresses ICN ubiquitination and degradation by interacting with Sel10.
  • This interaction disrupts the tumor-suppressive function of Sel10, promoting uncontrolled cell proliferation in KSHV-infected cells.
  • The LANA-Sel10-ICN axis represents a novel mechanism for KSHV-driven oncogenesis.

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