HAMLET Interacts with Histones and Chromatin in Tumor Cell Nuclei

Caroline Düringer, Ali Hamiche, Lotta Gustafsson, Hiroshi Kimura, Catharina Svanborg

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98 Citations (Scopus)

Abstract

HAMLET is a folding variant of human α-lactalbumin in an active complex with oleic acid. HAMLET selectively enters tumor cells, accumulates in their nuclei and induces apoptosis-like cell death. This study examined the interactions of HAMLET with nuclear constituents and identified histones as targets. HAMLET was found to bind histone H3 strongly and to lesser extent histones H4 and H2B. The specificity of these interactions was confirmed using BIAcore technology and chromatin assembly assays. In vivo in tumor cells, HAMLET co-localized with histones and perturbed the chromatin structure; HAMLET was found associated with chromatin in an insoluble nuclear fraction resistant to salt extraction. In vitro, HAMLET bound strongly to histones and impaired their deposition on DNA. We conclude that HAMLET interacts with histones and chromatin in tumor cell nuclei and propose that this interaction locks the cells into the death pathway by irreversibly disrupting chromatin organization.

Original languageEnglish
Pages (from-to)42131-42135
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
Publication statusPublished - 24 Oct 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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