RETRACTED: Selective cleavage of BLM, the Bloom syndrome protein, during apoptotic cell death (Retracted Article)

被引:23
作者
Bischof, O
Galande, S
Farzaneh, F
Kohwi-Shigematsu, T
Campisi, J
机构
[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
[2] Kings Coll London, Guys Kings & St Thomas Sch Med, Rayne Inst, Dept Mol Med, London SE5 9NU, England
关键词
D O I
10.1074/jbc.M006462200
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
Bloom syndrome (BS) is an autosomal recessive disorder characterized by a high incidence of cancer and genomic instability. BLM, the protein defective in BS, is a RECQ-like helicase that is presumed to function in mammalian DNA replication, recombination, or repair. We show here that BLM, but not the related RECQ-like helicase WRN, is rapidly cleaved in cells undergoing apoptosis. BLM was cleaved to 47- and 110-kDa major fragments, with kinetics similar to the apoptotic cleavage of poly(A)DP-ribose polymerase. BLM cleavage was prevented by a caspase 3 inhibitor and did not occur in caspase 3-deficient cells. Moreover, recombinant BLM was cleaved to 47- and 110-kDa fragments by caspase 3, but not caspase 6, in vitro. The caspase 3 recognition sequence (TEVD415)-T-412 was verified by mutating aspartate 415 to glycine and showing that this mutation rendered BLM resistant to caspase 3 cleavage. Cleavage did not abolish the BM helicase activity but abolished BLM nuclear foci and the association of BLM with condensed DNA and the insoluble matrix. The results suggest that BLM, but not WRN, is an early selected target during the execution of apoptosis.
引用
收藏
页码:12068 / 12075
页数:8
相关论文
共 70 条
[61]   APOPTOSIS IN THE PATHOGENESIS AND TREATMENT OF DISEASE [J].
THOMPSON, CB .
SCIENCE, 1995, 267 (5203) :1456-1462
[62]   A combinatorial approach defines specificities of members of the caspase family and granzyme B - Functional, relationships established for key mediators of apoptosis [J].
Thornberry, NA ;
Ranon, TA ;
Pieterson, EP ;
Rasper, DM ;
Timkey, T ;
GarciaCalvo, M ;
Houtzager, VM ;
Nordstrom, PA ;
Roy, S ;
Vaillancourt, JP ;
Chapman, KT ;
Nicholson, DW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (29) :17907-17911
[63]   Caspases and caspase inhibitors [J].
Villa, P ;
Kaufmann, SH ;
Earnshaw, WC .
TRENDS IN BIOCHEMICAL SCIENCES, 1997, 22 (10) :388-393
[64]   The nuclear matrix prepared by amine modification [J].
Wan, KM ;
Nickerson, JA ;
Krockmalnic, G ;
Penman, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :933-938
[65]  
Wang Y, 2000, GENE DEV, V14, P927
[66]   Genome stability - Failure to unwind causes cancer [J].
Watt, PM ;
Hickson, ID .
CURRENT BIOLOGY, 1996, 6 (03) :265-&
[67]   A METHOD FOR THE QUANTITATIVE RECOVERY OF PROTEIN IN DILUTE-SOLUTION IN THE PRESENCE OF DETERGENTS AND LIPIDS [J].
WESSEL, D ;
FLUGGE, UI .
ANALYTICAL BIOCHEMISTRY, 1984, 138 (01) :141-143
[68]   SIMIAN VIRUS-40 T-ANTIGEN DNA HELICASE IS A HEXAMER WHICH FORMS A BINARY COMPLEX DURING BIDIRECTIONAL UNWINDING FROM THE VIRAL ORIGIN OF DNA-REPLICATION [J].
WESSEL, R ;
SCHWEIZER, J ;
STAHL, H .
JOURNAL OF VIROLOGY, 1992, 66 (02) :804-815
[69]   Positional cloning of the Warner's syndrome gene [J].
Yu, CE ;
Oshima, J ;
Fu, YH ;
Wijsman, EM ;
Hisama, F ;
Alisch, R ;
Matthews, S ;
Nakura, J ;
Miki, T ;
Ouais, S ;
Martin, GM ;
Mulligan, J ;
Schellenberg, GD .
SCIENCE, 1996, 272 (5259) :258-262
[70]   A role for PML and the nuclear body in genomic stability [J].
Zong, S ;
Hu, P ;
Ye, TZ ;
Stan, R ;
Ellis, NA ;
Pandolfi, PP .
ONCOGENE, 1999, 18 (56) :7941-7947