دورية أكاديمية
Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes
| العنوان: | Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes |
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| المؤلفون: | Tang, QQ, Zhang, JW, Vinson, C, Lane, MD |
| بيانات النشر: | //www.pnas.org United States |
| سنة النشر: | 2004 |
| المجموعة: | University of Hong Kong: HKU Scholars Hub |
| مصطلحات موضوعية: | Cell Cycle, 3T3-L1 Cells, Adenoviridae - Genetics, Adipocytes - Cytology - Metabolism, Animals, Ccaat-Enhancer-Binding Protein-Beta - Chemistry - Metabolism, Ccaat-Enhancer-Binding Proteins - Chemistry - Genetics - Metabolism, Cell Differentiation, Cell Nucleus - Metabolism, Centromere - Metabolism, Genetic Vectors, Macromolecular Substances, Mice, Mitosis, Nuclear Localization Signals - Genetics, Stem Cells - Cytology - Metabolism |
| الوصف: | Hormonal induction of growth-arrested 3T3-L1 preadipocytes rapidly activates expression of CCAAT/enhancer-binding protein (C/EBP) β. Acquisition of DNA-binding activity by C/EBPβ, however, is delayed until the cells synchronously enter the S phase of mitotic clonal expansion (MCE). After MCE, C/EBPβ activates expression of C/EBPα and peroxisome proliferator-activated receptor γ, which then transcriptionally activate genes that give rise to the adipocyte phenotype. A-C/EBP, which possesses a leucine zipper but lacks functional DNA-binding and transactivation domains, forms stable inactive heterodimers with C/EBPβ in vitro. Infection of 3T3-L1 preadipocytes with an adenovirus A-C/EBP expression vector interferes with C/EBPβ function after induction of differentiation. A-C/EBP inhibited events associated with hormone-induced entry of S-phase of the cell cycle, including the turnover of p27/Kip1, a key cyclin-dependent kinase inhibitor, expression of cyclin A and cyclin-dependent kinase 2, DNA replication, MCE, and, subsequently, adipogenesis. Although A-C/EBP blocked cell proliferation associated with MCE, it did not inhibit normal proliferation of 3T3-L1 preadipocytes. Immunofluorescent staining of C/EBPβ revealed that A-C/EBP prevented the normal punctate nuclear staining of centromeres, an indicator of C/EBPβ binding to C/EBP regulatory elements in centromeric satellite DNA. The inhibitory effects of A-C/EBP appear to be due primarily to interference with nuclear import of C/EBPβ caused by obscuring its nuclear localization signal. These findings show that both MCE and adipogenesis are dependent on C/EBPβ. ; link_to_subscribed_fulltext |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0027-8424 |
| العلاقة: | Proceedings of the National Academy of Sciences of the United States of America; http://www.scopus.com/mlt/select.url?eid=2-s2.0-0346458703&selection=ref&src=s&origin=recordpageTest; Proceedings Of The National Academy Of Sciences Of The United States Of America, 2004, v. 101 n. 1, p. 43-47; 47; WOS:000187937200011; eid_2-s2.0-0346458703; 43; http://hdl.handle.net/10722/180721Test; 101 |
| DOI: | 10.1073/pnas.0307229101 |
| الإتاحة: | https://doi.org/10.1073/pnas.0307229101Test http://hdl.handle.net/10722/180721Test |
| رقم الانضمام: | edsbas.35B0119E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00278424 |
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| DOI: | 10.1073/pnas.0307229101 |