A minimal Bcl-x promoter is activated by Brn-3a and repressed by p53

被引：55

作者：

Sugars, KL

Budhram-Mahadeo, V

Packham, G

Latchman, DS

机构：

[1] UCL, Inst Child Hlth, Med Mol Biol Unit, London WC1N 1EH, England

[2] Univ Southampton, Sch Med, Div Canc Sci, CRC Wessex Med Oncol Unit, Southampton SO16 6YD, Hants, England

来源：

NUCLEIC ACIDS RESEARCH | 2001年 / 29卷 / 22期

关键词：

D O I：

10.1093/nar/29.22.4530

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 Brn-3a transcription factor stimulates the expression of the anti-apoptotic Bcl-2 and Bcl-x proteins and protects neuronal cells from apoptosis. Here we show that a minimal Bcl-x promoter is activated by Brn-3a and that this stimulation is prevented by the pro-apoptotic p53 protein. Both these effects are mediated via Bcl-x promoter sequences, which are indistinguishable from those required for minimal basal promoter activity. A newly described upstream Bcl-x promoter is also activated by Brn-3a with this activation being prevented by p53. Hence, Brn-3a-mediated activation of two distinct Bcl-x promoters and of the Bcl-2 promoter is blocked by p53 whereas this is not observed for Brn-3a activated promoters derived from genes not involved in inhibiting apoptosis. p53 therefore appears to specifically target the activation by Brn-3a of promoters derived from genes with an anti-apoptotic effect and this may be involved in the pro-apoptotic activity of p53.

引用

收藏

页码：4530 / 4540

页数：11

相关论文

共 30 条

[1] p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor [J].

Budhram-Mahadeo, V ;

Morris, PJ ;

Smith, MD ;

Midgley, CA ;

Boxer, LM ;

Latchman, DS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (21) :15237-15244

[2] ACTIVATION OF THE ALPHA-INTERNEXIN PROMOTER BY THE BRN-3A TRANSCRIPTION FACTOR IS DEPENDENT ON THE N-TERMINAL REGION OF THE PROTEIN [J].

BUDHRAMMAHADEO, V ;

MORRIS, PJ ;

LAKIN, ND ;

THEIL, T ;

CHING, GY ;

LILLYCROP, KA ;

MOROY, T ;

LIEM, RKH ;

LATCHMAN, DS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (06) :2853-2858

[3] TRANSCRIPTIONAL ACTIVATION BY P53 CORRELATES WITH SUPPRESSION OF GROWTH BUT NOT TRANSFORMATION [J].

CROOK, T ;

MARSTON, NJ ;

SARA, EA ;

VOUSDEN, KH .

CELL, 1994, 79 (05) :817-827

[4] The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis [J].

Ensor, E ;

Smith, MD ;

Latchman, DS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (07) :5204-5212

[5] Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development [J].

Erkman, L ;

McEvilly, RJ ;

Luo, L ;

Ryan, AK ;

Hooshmand, F ;

OConnell, SM ;

Keithley, EM ;

Rapaport, DH ;

Ryan, AF ;

Rosenfeld, MG .

NATURE, 1996, 381 (6583) :603-606

[6] BRN-3.0 - A POU-DOMAIN PROTEIN EXPRESSED IN THE SENSORY, IMMUNE, AND ENDOCRINE SYSTEMS THAT FUNCTIONS ON ELEMENTS DISTINCT FROM KNOWN OCTAMER MOTIFS [J].

GERRERO, MR ;

MCEVILLY, RJ ;

TURNER, E ;

LIN, CR ;

OCONNELL, S ;

JENNE, KJ ;

HOBBS, MV ;

ROSENFELD, MG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10841-10845

[7]

Gorman C., 1985, DNA CLONING PRACTICA, V1, P143

[8] ROLE OF BCL-2 IN THE SURVIVAL AND FUNCTION OF DEVELOPING AND MATURE SYMPATHETIC NEURONS [J].

GREENLUND, LJS ;

KORSMEYER, SJ ;

JOHNSON, EM .

NEURON, 1995, 15 (03) :649-661

[9]

Grillot DAM, 1997, J IMMUNOL, V158, P4750

[10] REGULATION OF NEURITE OUTGROWTH AND SNAP-25 GENE-EXPRESSION BY THE BRN-3A TRANSCRIPTION FACTOR [J].

LAKIN, ND ;

MORRIS, PJ ;

THEIL, T ;

SATO, TN ;

MOROY, T ;

WILSON, MC ;

LATCHMAN, DS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (26) :15858-15863