Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

被引：8

作者：

Hudson, C. D. ^{[1
]}

Sayan, A. E. ^{[2
]}

Melino, G. ^{[2
,3
]}

Knight, R. A. ^{[3
]}

Latchman, D. S. ^{[1
]}

Budhram-Mahadeo, V. ^{[1
]}

机构：

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

[2] Univ Roma Tor Vergata, Dept Expt Med, IRCCS, Biochem Lab IDI, Rome, Italy

[3] MRC, Toxicol Unit, Leicester, Leics, England

来源：

CELL DEATH AND DIFFERENTIATION | 2008年 / 15卷 / 08期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

apoptosis; Brn-3a; POU4F1; neuronal differentiation; p73; transcription;

D O I：

10.1038/cdd.2008.45

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/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon interaction with other proteins. In this study, we demonstrated the physical interaction of Brn-3a with different p73 isoforms and showed co-localization in sensory neurons arising from the neural crest. The biological effects of p73/Brn-3a interaction depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and DNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but cooperated to increase transcription of the cell cycle regulator p21(CIP1/Waf1). The region 425-494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21(CIP1/Waf1) promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21(CIP1/Waf1) promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors.

引用

页码：1266 / 1278

页数：13

共 43 条

[11] The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis
Ensor, E
Smith, MD
Latchman, DS
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (07) : 5204 - 5212
[12] Distinct domains of Brn-3a regulate apoptosis and neurite outgrowth in vivo
Faulkes, DJ
Ensor, E
Le Rouzic, E
Latchman, DS
[J]. NEUROREPORT, 2004, 15 (09) : 1421 - 1425
[13] BRN-3.0 EXPRESSION IDENTIFIES EARLY POSTMITOTIC CNS NEURONS AND SENSORY NEURAL PRECURSORS
FEDTSOVA, NG
TURNER, EE
[J]. MECHANISMS OF DEVELOPMENT, 1995, 53 (03) : 291 - 304
[14] p63 and p73 are required for p53-dependent apoptosis in response to DNA damage
Flores, ER
Tsai, KY
Crowley, D
Sengupta, S
Yang, A
McKeon, F
Jacks, T
[J]. NATURE, 2002, 416 (6880) : 560 - 564
[15] Greenwood AL, 1999, DEVELOPMENT, V126, P3545
[16] Human ΔNp73 regulates a dominant negative feedback loop for TAp73 and p53
Grob, TJ
Novak, U
Maisse, C
Barcaroli, D
Lüthi, AU
Pirnia, F
Hügli, B
Graber, HU
De Laurenzi, V
Fey, MF
Melino, G
Tobler, A
[J]. CELL DEATH AND DIFFERENTIATION, 2001, 8 (12) : 1213 - 1223
[17] Huang EJ, 1999, DEVELOPMENT, V126, P2869
[18] Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate
Hudson, CD
Morris, PJ
Latchman, DS
Budhram-Mahadeo, VS
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (12) : 11851 - 11858
[19] Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis
Hudson, CD
Podesta, J
Henderson, D
Latchman, DS
Budhram-Mahadeo, V
[J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2004, 78 (06) : 803 - 814
[20] p73: Structure and function
Ichimiya, S
Nakagawara, A
Sakuma, Y
Kimura, S
Ikeda, T
Satoh, M
Takahashi, N
Sato, N
Mori, M
[J]. PATHOLOGY INTERNATIONAL, 2000, 50 (08) : 589 - 593

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