Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells

被引：241

作者：

Polo, JM

Dell'Oso, T

Ranuncolo, SM

Cerchietti, L

Beck, D

Da Silva, GF

Prive, GG

Licht, JD

Melnick, A

机构：

[1] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA

[2] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[3] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA

来源：

NATURE MEDICINE | 2004年 / 10卷 / 12期

关键词：

D O I：

10.1038/nm1134

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：

The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional and biological properties, we generated a peptide that specifically binds BCL6 and blocks corepressor recruitment in vivo. This inhibitor disrupts BCL6-mediated repression and establishment of silenced chromatin, reactivates natural BCL6 target genes, and abrogates BCL6 biological function in B cells. In BCL6-positive lymphoma cells, peptide blockade caused apoptosis and cell cycle arrest. BTB domain peptide inhibitors may constitute a novel therapeutic agent for B-cell lymphomas.

引用

收藏

页码：1329 / 1335

页数：7

相关论文

共 33 条

[1] Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain [J].

Ahmad, KF ;

Melnick, A ;

Lax, S ;

Bouchard, D ;

Liu, J ;

Kiang, CL ;

Mayer, S ;

Takahashi, S ;

Licht, JD ;

Privé, GG .

MOLECULAR CELL, 2003, 12 (06) :1551-1564

[2] Ambivalent role of BCL6 in cell survival and transformation [J].

Albagli-Curiel, O .

ONCOGENE, 2003, 22 (04) :507-516

[3] BCL-6 expression during B-cell activation [J].

Allman, D ;

Jain, A ;

Dent, A ;

Maile, RR ;

Selvaggi, T ;

Kehry, MR ;

Staudt, LM .

BLOOD, 1996, 87 (12) :5257-5268

[4] A RAPID MICROPREPARATION TECHNIQUE FOR EXTRACTION OF DNA-BINDING PROTEINS FROM LIMITING NUMBERS OF MAMMALIAN-CELLS [J].

ANDREWS, NC ;

FALLER, DV .

NUCLEIC ACIDS RESEARCH, 1991, 19 (09) :2499-2499

[5] A TRANSCRIPTIONAL CO-REPRESSOR THAT INTERACTS WITH NUCLEAR HORMONE RECEPTORS [J].

CHEN, JD ;

EVANS, RM .

NATURE, 1995, 377 (6548) :454-457

[6] ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cefl lymphorna oncoprotein [J].

Chevallier, N ;

Corcoran, CM ;

Lennon, C ;

Hyjek, E ;

Chadburn, A ;

Bardwell, VJ ;

Licht, JD ;

Melnick, A .

BLOOD, 2004, 103 (04) :1454-1463

[7] Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors:: The case of HIC-1 and γFBP-B [J].

Deltour, S ;

Guerardel, C ;

Leprince, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :14831-14836

[8] Control of inflammation, cytokine expression, and germinal center formation by BCL-6 [J].

Dent, AL ;

Shaffer, AL ;

Yu, X ;

Allman, D ;

Staudt, LM .

SCIENCE, 1997, 276 (5312) :589-592

[9] MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation [J].

Fujita, N ;

Jaye, DL ;

Geigerman, C ;

Akyildiz, A ;

Mooney, MR ;

Boss, JM ;

Wade, PA .

CELL, 2004, 119 (01) :75-86

[10] Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4 [J].

Gupta, S ;

Jiang, M ;

Anthony, A ;

Pernis, AB .

JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (12) :1837-1848

← 1 2 3 4 →