Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Carcinoma, Small Cell
  • HSP90 Heat-Shock Proteins
  • Lung Neoplasms

abstract

  • The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compounds, we have discovered that small-cell lung carcinoma is a distinctive cellular system in which apoptosis is mainly regulated by Hsp90. Unlike the well-characterized antiapoptotic chaperone Hsp70, Hsp90 is not a general inhibitor of apoptosis, but it assumes this role in systems such as small-cell lung carcinoma, in which apoptosis is uniquely dependent on and effected through the intrinsic pathway, without involvement of caspase elements upstream of mitochondria or alternate pathways that are not apoptosome-channeled. These results provide important evidence for a transformation-specific interplay between chaperones in regulating apoptosis in malignant cells.

publication date

  • January 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/nchembio.2007.10

PubMed ID

  • 17603540

Additional Document Info

start page

  • 498

end page

  • 507

volume

  • 3

number

  • 8