HAMLET interacts with histones and chromatin in tumor cell nuclei

被引:99
作者
Düringer, C
Hamiche, A
Gustafsson, L
Kimura, H
Svanborg, C
机构
[1] Lund Univ, Inst Lab Med, Sect Microbiol Immunol & Glycobiol, S-22362 Lund, Sweden
[2] Inst Andre Lwoff, CNRS, UPR 9079, Equipe Fonct & Dynam Chromatine, F-94800 Villejuif, France
[3] Tokyo Med & Dent Univ, Inst Med Res, Dept Funct Genom, Bunkyo Ku, Tokyo 1138510, Japan
关键词
D O I
10.1074/jbc.M306462200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
HAMLET is a folding variant of human alpha-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.
引用
收藏
页码:42131 / 42135
页数:5
相关论文
共 19 条
[1]  
AUSUBEL FH, 1993, CURRENT PROTOCOLS MO, V2, P12
[2]   STABILITY OF THE HIGHER-ORDER STRUCTURE OF CHICKEN-ERYTHROCYTE CHROMATIN IN SOLUTION [J].
BATES, DL ;
BUTLER, PJG ;
PEARSON, EC ;
THOMAS, JO .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1981, 119 (03) :469-476
[3]   APOPTOSIS INDUCED BY A HUMAN-MILK PROTEIN [J].
HAKANSSON, A ;
ZHIVOTOVSKY, B ;
ORRENIUS, S ;
SABHARWAL, H ;
SVANBORG, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :8064-8068
[4]   Multimeric α-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei [J].
Håkansson, A ;
Andréasson, J ;
Zhivotovsky, B ;
Karpman, D ;
Orrenius, S ;
Svanborg, C .
EXPERIMENTAL CELL RESEARCH, 1999, 246 (02) :451-460
[5]   The switch in the helical handedness of the histone (H3-H4)2 tetramer within a nucleoprotein particle requires a reorientation of the H3-H3 interface [J].
Hamiche, A ;
Richard-Foy, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (15) :9261-9269
[6]   Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF [J].
Hamiche, A ;
Kang, JG ;
Dennis, C ;
Xiao, H ;
Wu, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (25) :14316-14321
[7]   BINDING MODE OF NUCLEOSOME-ASSEMBLY PROTEIN (AP-I) AND HISTONES [J].
ISHIMI, Y ;
KOJIMA, M ;
YAMADA, M ;
HANAOKA, F .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1987, 162 (01) :19-24
[8]   Chromatin assembly factors: a dual function in nucleosome formation and mobilization? [J].
Ito, T ;
Tyler, JK ;
Kadonaga, LT .
GENES TO CELLS, 1997, 2 (10) :593-600
[9]   Apoptosis: A link between cancer genetics and chemotherapy [J].
Johnstone, RW ;
Ruefli, AA ;
Lowe, SW .
CELL, 2002, 108 (02) :153-164
[10]   APOPTOSIS - BASIC BIOLOGICAL PHENOMENON WITH WIDE-RANGING IMPLICATIONS IN TISSUE KINETICS [J].
KERR, JFR ;
WYLLIE, AH ;
CURRIE, AR .
BRITISH JOURNAL OF CANCER, 1972, 26 (04) :239-+