共查询到20条相似文献,搜索用时 531 毫秒
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Werten S Mitschler A Romier C Gangloff YG Thuault S Davidson I Moras D 《The Journal of biological chemistry》2002,277(47):45502-45509
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Thuault S Gangloff YG Kirchner J Sanders S Werten S Romier C Weil PA Davidson I 《The Journal of biological chemistry》2002,277(47):45510-45517
Yeast TFIID comprises the TATA binding protein and 14 TBP-associated factors (TAF(II)s), nine of which contain histone-fold domains (HFDs). The C-terminal region of the TFIID-specific yTAF4 (yTAF(II)48) containing the HFD shares strong sequence similarity with Drosophila (d)TAF4 (dTAF(II)110) and human TAF4 (hTAF(II)135). A structure/function analysis of yTAF4 demonstrates that the HFD, a short conserved C-terminal domain (CCTD), and the region separating them are all required for yTAF4 function. Temperature-sensitive mutations in the yTAF4 HFD alpha2 helix or the CCTD can be suppressed upon overexpression of yTAF12 (yTAF(II)68). Moreover, coexpression in Escherichia coli indicates direct yTAF4-yTAF12 heterodimerization optimally requires both the yTAF4 HFD and CCTD. The x-ray crystal structure of the orthologous hTAF4-hTAF12 histone-like heterodimer indicates that the alpha3 region within the predicted TAF4 HFD is unstructured and does not correspond to the bona fide alpha3 helix. Our functional and biochemical analysis of yTAF4, rather provides strong evidence that the HFD alpha3 helix of the TAF4 family lies within the CCTD. These results reveal an unexpected and novel HFD organization in which the alpha3 helix is separated from the alpha2 helix by an extended loop containing a conserved functional domain. 相似文献
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Human mesenchymal stem cells (hMSCs) are able to self-replicate and differentiate into a variety of cell types including osteoblasts,
chondrocytes, adipocytes, endothelial cells, and muscle cells. It was reported that fibroblast growth factor-2 (FGF-2) increased
the growth rate and multidifferentiation potentials of hMSCs. In this study, we investigated the genes involved in the promotion
of osteogenic and chondrogenic differentiation potentials of hMSCs in the presence of FGF-2. hMSCs were maintained in the
medium with FGF-2. hMSCs were harvested for the study of osteogenic or chondrogenic differentiation potential after 15 days’
culture. To investigate osteogenic differentiation, the protein levels of alkaline phosphatase (ALP) and the mRNA expression
levels of osteocalcin were measured after the induction of osteogenic differentiation. Moreover, the investigation for chondrogenic
differentiation was performed by measuring the mRNA expression levels of type II and type X collagens after the induction
of chondrogenic differentiation. The expression levels of ALP, type II collagen, and type X collagen of hMSCs cultured with
FGF-2 were significantly higher than control. These results suggested that FGF-2 increased osteogenic and chondrogenic differentiation
potentials of hMSCs. Furthermore, microarray analysis was performed after 15 days’ culture in the medium with FGF-2. We found
that the overall insulin-like growth factor-I (IGF-I) and transforming growth factor-β (TGF-β) signaling pathways were inactivated
by FGF-2. These results suggested that the inactivation of IGF-I and TGF-β signaling promotes osteogenic and chondrogenic
differentiation potential of hMSCs in the presence of FGF-2. 相似文献
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Ana M. Sotoca Jose Roelofs-Hendriks Sjef Boeren Peter M. van der Kraan Jacques Vervoort Everardus J.J. van Zoelen Ester Piek 《Experimental cell research》2013
This is the first study that comprehensively describes the effects of the platelet-derived growth factor (PDGF) isoforms C and D during in vitro expansion of human mesenchymal stem cells (hMSCs). Our results show that PDGFs can enhance proliferation of hMSCs without affecting their multipotency. It is of great value to culture and expand hMSCs in a safe and effective manner without losing their multipotency for manipulation and further development of cell-based therapies. Moreover, differential effects of PDGF isoforms have been observed on lineage-specific differentiation induced by BMP2 and Vitamin D3. Based on label-free LC-based quantitative proteomics approach we have furthermore identified specific pathways induced by PDGFs during the proliferation process, showing the importance of bioinformatics tools to study cell function. 相似文献
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Pallavi Mantina Lindsay MacDonald Adam Kulaga Lina Zhao Dave Hansen 《Mechanisms of development》2009,126(5-6):417-429
Dividing stem cells can give rise to two types of daughter cells; self-renewing cells that have virtually the same properties as the parent cell, and differentiating cells that will eventually form part of a tissue. The Caenorhabditis elegans germ line serves as a model to study how the balance between these two types of daughter cells is maintained. A mutation in teg-4 causes over-proliferation of the stem cells, thereby disrupting the balance between proliferation and differentiation. We have cloned teg-4 and found it to encode a protein homologous to the highly conserved splicing factor subunit 3 of SF3b. Our allele of teg-4 partially reduces TEG-4 function. In an effort to determine how teg-4 functions in controlling stem cell proliferation, we have performed genetic epistasis analysis with known factors controlling stem cell proliferation. We found that teg-4 is synthetic tumorous with genes in both major redundant genetic pathways that function downstream of GLP-1/Notch signaling to control the balance between proliferation and differentiation. Therefore, teg-4 is unlikely to function specifically in either of these two genetic pathways. Further, the synthetic tumorous phenotype seen with one of the genes from these pathways is epistatic to glp-1, indicating that teg-4 functions downstream of glp-1, likely as a positive regulator of meiotic entry. We propose that a reduction in teg-4 activity reduces the splicing efficiency of targets involved in controlling the balance between proliferation and differentiation. This results in a shift in the balance towards proliferation, eventually forming a germline tumor. 相似文献
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Two novel Drosophila TAF(II)s have homology with human TAF(II)30 and are differentially regulated during development
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Georgieva S Kirschner DB Jagla T Nabirochkina E Hanke S Schenkel H de Lorenzo C Sinha P Jagla K Mechler B Tora L 《Molecular and cellular biology》2000,20(5):1639-1648
TFIID is a multiprotein complex composed of the TATA binding protein (TBP) and TBP-associated factors (TAF(II)s). The binding of TFIID to the promoter is the first step of RNA polymerase II preinitiation complex assembly on protein-coding genes. Yeast (y) and human (h) TFIID complexes contain 10 to 13 TAF(II)s. Biochemical studies suggested that the Drosophila (d) TFIID complexes contain only eight TAF(II)s, leaving a number of yeast and human TAF(II)s (e.g., hTAF(II)55, hTAF(II)30, and hTAF(II)18) without known Drosophila homologues. We demonstrate that Drosophila has not one but two hTAF(II)30 homologues, dTAF(II)16 and dTAF(II)24, which are encoded by two adjacent genes. These two genes are localized in a head-to-head orientation, and their 5' extremities overlap. We show that these novel dTAF(II)s are expressed and that they are both associated with TBP and other bona fide dTAF(II)s in dTFIID complexes. dTAF(II)24, but not dTAF(II)16, was also found to be associated with the histone acetyltransferase (HAT) dGCN5. Thus, dTAF(II)16 and dTAF(II)24 are functional homologues of hTAF(II)30, and this is the first demonstration that a TAF(II)-GCN5-HAT complex exists in Drosophila. The two dTAF(II)s are differentially expressed during embryogenesis and can be detected in both nuclei and cytoplasm of the cells. These results together indicate that dTAF(II)16 and dTAF(II)24 may have similar but not identical functions. 相似文献
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