Abstract:
:Essential for embryonic development, the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in breast and prostate cancers and is implicated in the growth and aggression of the tumors. The tumorigenic mechanism underlying EZH2 overexpression is largely unknown. It is believed that EZH2 exerts its biological activity as a transcription repressor. However, we report here that EZH2 functions in gene transcriptional activation in breast cancer cells. We show that EZH2 transactivates genes that are commonly targeted by estrogen and Wnt signaling pathways. We demonstrated that EZH2 physically interacts directly with estrogen receptor alpha and beta-catenin, thus connecting the estrogen and Wnt signaling circuitries, functionally enhances gene transactivation by estrogen and Wnt pathways, and phenotypically promotes cell cycle progression. In addition, we identified the transactivation activity of EZH2 in its two N-terminal domains and demonstrated that these structures serve as platforms to connect transcription factors and the Mediator complex. Our experiments indicated that EZH2 is a dual function transcription regulator with a dynamic activity, and we provide a mechanism for EZH2 in tumorigenesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Shi B,Liang J,Yang X,Wang Y,Zhao Y,Wu H,Sun L,Zhang Y,Chen Y,Li R,Zhang Y,Hong M,Shang Ydoi
10.1128/MCB.00162-07subject
Has Abstractpub_date
2007-07-01 00:00:00pages
5105-19issue
14eissn
0270-7306issn
1098-5549pii
MCB.00162-07journal_volume
27pub_type
杂志文章abstract::Multiple biological functions have been ascribed to the Ras-related G protein R-Ras. These include the ability to transform NIH 3T3 fibroblasts, the promotion of cell adhesion, and the regulation of apoptotic responses in hematopoietic cells. To investigate the signaling mechanisms responsible for these biological phe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6333
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.10.3510-3521.2000
更新日期:2000-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00419-07
更新日期:2007-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.1.235
更新日期:1995-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1111
更新日期:1987-03-01 00:00:00
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更新日期:1998-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2020-01-03 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.3663
更新日期:1997-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.1.528
更新日期:1987-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2000-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2004-10-01 00:00:00
abstract::alpha 1-Antitrypsin (AT), the major elastase inhibitor in mammalian serum, is produced primarily in the liver. We have characterized AT gene structure and expression in the mouse species Mus caroli, which expresses high levels of AT in the kidneys as well as in the liver. Analysis of cDNA and genomic clones showed tha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.8.4605
更新日期:1998-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2540-2549.2006
更新日期:2006-04-01 00:00:00
abstract::Cellular senescence is a tumor-suppressive process characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated beta-galactosidase (SA-beta-Gal). We report here a role for CDK5 in induction of senescent cytoskeletal changes. CDK5 activation is upregulated in senescing ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2004-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2977
更新日期:1987-08-01 00:00:00
abstract::The oncogene product of the avian sarcoma virus CT10, P47gag-crk, contains the SH2, SH2', and SH3 domains and binds proteins in a phosphotyrosine (ptyr)-dependent manner. In this study, we have determined the region of P47gag-crk essential for binding to ptyr-containing proteins. Mutant P47gag-crk proteins expressed i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1607
更新日期:1991-03-01 00:00:00
abstract::A cDNA encoding a novel Krüppel-type zinc finger protein, FKLF, was cloned from fetal globin-expressing human fetal erythroid cells. The deduced polypeptide sequence composed of 512 amino acids revealed that, like Sp1 and EKLF, FKLF has three contiguous zinc fingers at the near carboxyl-terminal end. A long amino-term...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3571
更新日期:1999-05-01 00:00:00