Suppression of β-amyloid precursor protein signaling into the nucleus by estrogens mediated through complex formation between the estrogen receptor and Fe65

被引:26
作者
Bao, Junying [1 ]
Cao, Chuanhai [1 ]
Zhang, Xiaohui [1 ]
Jiang, Feng [1 ]
Nicosia, Santo V. [1 ]
Bai, Wenlong [1 ]
机构
[1] Univ S Florida, Coll Med, Dept Pathol, Tampa, FL 33612 USA
关键词
D O I
10.1128/MCB.01280-06
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 C-terminal fragment of the beta-amyloid precursor protein produced after cleavage by gamma-secretase, namely, APPct or AICD, has been shown to form a multimeric complex with the adaptor protein Fe65 and to regulate transcription through the recruitment of the histone acetyltransferase Tip60. The present study shows that 17 beta-estradiol inhibits the transcriptional and apoptotic activities of the APPct complex by a process involving the interaction of estrogen receptor alpha (ER alpha) with Fe65. ER alpha-Fe65 complexes were detected both in vitro and in the mouse brain, and recruitment of ER alpha to the promoter of an APPct target gene (KAI1) was demonstrated. Our studies reveal a novel mechanism of estrogen action, which may explain the well-known neuroprotective functions of estrogens as well as the complex role of this female hormone in the pathogenesis of neuronal degeneration diseases.
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收藏
页码:1321 / 1333
页数:13
相关论文
共 53 条
  • [1] Estrogen exerts neuroprotective effects via membrane estrogen receptors and rapid Akt/NOS activation
    Alexaki, VI
    Charalampopoulos, I
    Kampa, M
    Vassalou, H
    Theodoropoulos, P
    Stathopoulos, EN
    Hatzoglou, A
    Gravanis, A
    Castanas, E
    [J]. FASEB JOURNAL, 2004, 18 (11) : 1594 - +
  • [2] Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and β-amyloid precursor protein
    Baek, SH
    Ohgi, KA
    Rose, DW
    Koo, EH
    Glass, CK
    Rosenfeld, MG
    [J]. CELL, 2002, 110 (01) : 55 - 67
  • [3] Tip60 is a nuclear hormone receptor coactivator
    Brady, ME
    Ozanne, DM
    Gaughan, L
    Waite, I
    Cook, S
    Neal, DE
    Robson, CN
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) : 17599 - 17604
  • [4] A transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60
    Cao, XW
    Südhof, TC
    [J]. SCIENCE, 2001, 293 (5527) : 115 - 120
  • [5] Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II
    Chang, A
    Cheang, S
    Espanel, X
    Sudol, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) : 20562 - 20571
  • [6] Induction of antioxidative and antiapoptotic thioredoxin supports neuroprotective hypothesis of estrogen
    Chiueh, CC
    Lee, SY
    Andoh, T
    Murphy, DL
    [J]. ENDOCRINE, 2003, 21 (01) : 27 - 31
  • [7] Dodart JC, 2000, REV NEUROSCIENCE, V11, P75
  • [8] Genomic organization of the human KAl1 metastasis-suppressor gene
    Dong, JT
    Isaacs, WB
    Barrett, JC
    Isaacs, JT
    [J]. GENOMICS, 1997, 41 (01) : 25 - 32
  • [9] Estrogen receptor α, not β, is a critical link in estradiol-mediated protection against brain injury
    Dubal, DB
    Zhu, H
    Yu, J
    Rau, SW
    Shughrue, PJ
    Merchenthaler, I
    Kindy, MS
    Wise, PM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) : 1952 - 1957
  • [10] Conjugated equine estrogens and global cognitive function in postmenopausal women - Women's Health Initiative Memory Study
    Espeland, MA
    Rapp, SR
    Shumaker, SA
    Brunner, R
    Manson, JE
    Sherwin, BB
    Hsia, J
    Margolis, KL
    Hogan, PE
    Wallace, R
    Dailey, M
    Freeman, R
    Hays, J
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 291 (24): : 2959 - 2968