共查询到20条相似文献,搜索用时 31 毫秒
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Dong J Huang S Caikovski M Ji S McGrath A Custorio MG Creighton CJ Maliakkal P Bogoslovskaia E Du Z Zhang X Lewis MT Sablitzky F Brisken C Li Y 《Development (Cambridge, England)》2011,138(23):5247-5256
The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity. 相似文献
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Prior to puberty the Sertoli cells undergo active cell proliferation, and at the onset of puberty they become a terminally differentiated postmitotic cell population that support spermatogenesis. The molecular mechanisms involved in the postmitotic block of pubertal and adult Sertoli cells are unknown. The four known helix-loop-helix ID proteins (i.e., Id1, Id2, Id3, and Id4) are considered dominant negative regulators of cellular differentiation pathways and act as positive regulators of cellular proliferation. ID proteins are expressed at low levels by postpubertal Sertoli cells and are transiently induced by serum. The hypothesis tested was that ID proteins can induce a terminally differentiated postmitotic Sertoli cell to reenter the cell cycle if they are constitutively expressed. To test this hypothesis, ID1 and ID2 were stably integrated and individually overexpressed in postmitotic rat Sertoli cells. Overexpression of ID1 or ID2 allowed postmitotic Sertoli cells to reenter the cell cycle and undergo mitosis. The cells continued to proliferate even after 300 cell doublings. The functional markers of Sertoli cell differentiation such as transferrin, inhibin alpha, Sert1, and androgen binding protein (ABP) continued to be expressed by the proliferating Sertoli cells, but at lower levels. FSH receptor expression was lost in the proliferating Sertoli cell-Id lines. Some Sertoli cell genes, such as cyclic protein 2 (cathepsin L) and Sry-related HMG box protein-11 (Sox11) increase in expression. At no stage of proliferation did the cells exhibit senescence. The expression profile as determined with a microarray protocol of the Sertoli cell-Id lines suggested an overall increase in cell cycle genes and a decrease in growth inhibitory genes. These results demonstrate that overexpression of ID1 and ID2 genes in a postmitotic, terminally differentiated cell type have the capacity to induce reentry into the cell cycle. The observations are discussed in regards to potential future applications in model systems of terminally differentiated cell types such as neurons or myocytes. 相似文献
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Olig1, a member of class B basic-helix-loop-helix (bHLH), plays key roles in early oligodendrocyte specification. Inhibitors
of DNA binding (Id) is another sub-class of HLH proteins, act as dominant-negative regulators of bHLH proteins, which can
form heterodimers with class A or B bHLH proteins, but lack the critical basic DNA binding domain. Id4 was recently found
to interact with olig1 and inhibit oligodendrocyte differentiation. However, there still no direct evidence to reveal the
spatial and temporal interaction of olig1 and ID4 in living cells. In this study, we performed bimolecular fluorescence complementation
(BiFC) analysis to further characterize the distinct subcellular localization of olig1, ID4 and their dimer in living SW1116
cells. To examine the subcellular localization of olig1 and ID4 by themselves, the olig1-EGFP or ID4-DsRed2 fusion proteins
were also expressed in SW1116 cells, respectively. As predicted, the olig1-EGFP fusion proteins were located in the nucleus,
and ID4-DsRed2 fusion proteins were located in the cytoplasm. When olig1-EGFP and ID4-DsRed2 fusion proteins were co-expressed,
the green and red signals were co-located in the cytoplasm. Using BiFC, the strong BiFC signals could be detected in pBiFC-olig1VN173
and pBiFC-ID4VC155 co-transfected cells and the fluorescence signal was located in the cytoplasm. These results collectively
confirmed that olig1 and ID4 could interact and form dimer in living cells, and ID4 could block the transport of olig1 from
cytoplasm to nucleus. 相似文献
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Expression of ID family genes in the synovia from patients with rheumatoid arthritis 总被引:2,自引:0,他引:2
Sakurai D Yamaguchi A Tsuchiya N Yamamoto K Tokunaga K 《Biochemical and biophysical research communications》2001,284(2):436-442
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by aggressive proliferation of synovial tissue leading to destruction of cartilage and bone. To identify molecules which play a crucial role for the pathogenesis, we compared mRNA expression pattern of RA synovium with that of osteoarthritis (OA), using the differential display. From the panel of differentially expressed genes, ID1 (inhibitor of differentiation 1) was considered to be particularly relevant to the pathogenesis of RA, because Id family genes have been shown to play a role in cell proliferation and angiogenesis. To examine whether the up-regulation of these genes is consistently observed in the patients with RA, mRNA levels of ID1 and ID3 in the synovial tissues from 13 patients with RA and 6 patients with OA were semi-quantitatively analyzed by RT-PCR. Mean mRNA levels of ID1 and ID3 were significantly elevated in RA synovia compared with OA by 8.6-fold (P = 0.0044) and 3.3-fold (P = 0.0085), respectively. Immunohistochemistry revealed striking staining of Id1 and Id3 in the endothelial cells, suggesting a possible role of Id in severe angiogenesis observed in RA. The expression of Id family genes in the synovium constitutes a new finding of particular interest. Their functional role as well as their contribution to the genetic susceptibility to RA requires further investigation. 相似文献
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Bone morphogenetic protein (BMP)-4 signalling leads to the direct upregulation of ID3 proto-oncogene expression in human ovarian cancer cells. An upstream BMP4-responsive enhancer element consisting of a palindromic BMP response element (BRE) site and CAGA box was identified ~3.0 kb upstream of the human ID3 gene, and a nearly-identical element exists in the second intron of the ID3 gene. BMP4 stimulation leads to the direct binding of Smads 1/5 and Smad4 to the upstream and intronic enhancers, and together both enhancers cooperate to yield heightened BMP4-mediated ID3 promoter activity. We further demonstrate that ID3 is overexpressed in human ovarian cancer cells when compared to normal ovarian surface epithelial cells, and treatment of ovarian cancer cells with the BMP4 antagonist Noggin abrogates endogenous ID3 gene expression. Our findings define the mechanism of BMP4-mediated ID3 gene expression, and support the notion that ovarian cancer cells possess autocrine BMP4 signalling required to sustain ID3 overexpression which may contribute to human ovarian cancer pathogenesis. 相似文献
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The Id4 HLH protein and the timing of oligodendrocyte differentiation 总被引:10,自引:0,他引:10
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