Mol Cell Biol 2010,
PMID: 20086099
Wang, Bing; Liu, Kang; Lin, Hui-Yi; Bellam, Naresh; Ling, Shiyun; Lin, Weei-Chin
14-3-3 proteins regulate many cellular functions, including proliferation. However, the detailed mechanisms by which they control the cell cycle remain to be fully elucidated. We report that one of the 14-3-3 isoforms, 14-3-3tau, is required for the G(1)/S transition through its role in ubiquitin-independent proteasomal degradation of p21. 14-3-3tau binds to p21, MDM2, and the C8 subunit of the 20S proteasome in G(1) phase and facilitates proteasomal targeting of p21. This function of 14-3-3tau may be deregulated in cancer. The overexpression of 14-3-3tau is frequently found in primary human breast cancer and correlates with lower levels of p21 and shorter patient survival. Tenascin-C, an extracellular matrix protein involved in tumor initiation and progression and a known 14-3-3tau inducer, decreases p21 and abrogates adriamycin-induced G(1)/S arrest. It has been known that p21 is required for a proper tamoxifen response in breast cancer. We show that the overexpression of 14-3-3tau inhibits tamoxifen-induced p21 induction and growth arrest in MCF7 cells. Together, the findings of our studies strongly suggest a novel oncogenic role of 14-3-3tau by downregulating p21 in breast cancer. Therefore, 14-3-3tau may be a potential therapeutic target in breast cancer.
Diseases/Pathways annotated by Medline MESH: Breast Neoplasms
Document information provided by NCBI PubMed
Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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IRef Biogrid Interaction:
YWHAQ
—
MDM2
(direct interaction, pull down)
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IRef Biogrid Interaction:
YWHAQ
—
MDM2
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
CDKN1A
—
MDM2
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
YWHAQ
—
PSMA3
(direct interaction, pull down)
-
IRef Biogrid Interaction:
YWHAQ
—
PSMA3
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
YWHAQ
—
CDKN1A
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
YWHAQ
—
CDKN1A
(direct interaction, pull down)
-
IRef Biogrid Interaction:
CDKN1A
—
PSMA3
(direct interaction, pull down)
-
IRef Biogrid Interaction:
CDKN1A
—
PSMA3
(physical association, affinity chromatography technology)
In total, 5 gene pairs are associated to this article in curated databases