Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Special AT-rich sequence-binding protein 1 (SATB1), predominantly expressed in thymocytes, was identified as a component of the nuclear matrix protein fraction. Programmed cell death of Jurkat T-cells was induced by various stimuli in Fas-dependent and -independent fashion. During apoptosis, but not during necrosis, SATB1 was cleaved, as rapidly as was lamin B, in a caspase-dependent way yielding a stable 70 kDa fragment. The same result was obtained for apoptotic HL60-cells. We constructed various deletion constructs of SATB1, expressing protein chimeras tagged with green fluorescent protein (GFP). Transient transfection of these into Jurkat or HeLa cells followed by initiation of apoptosis allowed us to map the potential caspase-6 cleavage site VEMD to the N-terminal third of SATB1, leaving an intact DNA-binding domain in the C-terminal part of the protein. Our results suggest that apoptosis-specific breakdown of SATB1, a transcriptional activator of the CD8a gene, might be of physiological relevance during thymic clonal deletion and apoptosis of peripheral T-lymphoid cells.
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PMID:The fate of the nuclear matrix-associated-region-binding protein SATB1 during apoptosis. 1080 76

TLS/FUS is a nucleic acid-binding protein whose N-terminal half functions as a transcriptional activator domain in fusion oncoproteins found in human leukemias and liposarcomas. Previous reports have suggested a role for TLS/FUS in transcription and splicing processes. Here we report the association of TLS/FUS with the nuclear matrix and investigate its role in splicing. Splicing of two pre-mRNAs was inhibited in a TLS/FUS-immunodepleted extract and could only be partly restored by addition of recombinant TLS/FUS or/and SR proteins, known interaction partners of TLS/FUS. The subsequent analysis of TLS/FUS immunoprecipitates revealed that, in addition to the SR proteins SC35 and SRp75, the splicing factor PTB (hnRNPI) and the splicing coactivator SRm160 are complexed with TLS/FUS, thus explaining the inability to restore splicing completely. Coimmunolocalization confirmed the nuclear matrix association and interaction of TLS/FUS with PTB, SR proteins, and SRm160. Our results suggest that the matrix protein TLS/FUS plays a role in spliceosome assembly.
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PMID:Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. 1258 38

Although much has been learned about growth plate development and chondrocyte gene expression during cellular maturation and matrix remodeling in the mouse, there has been a limited study of the interrelationships of gene expression between proteinases, growth factors, and other regulatory molecules in the mouse and in other species. Here we use RT-PCR of sequential transverse sections to examine the expression profiles of genes involved in chondrocyte growth, differentiation, matrix assembly, remodeling, and mineralization in the bovine proximal tibial growth plate. Specifically, we studied the expression of genes encoding COL2A1 and COL10A1, the latter a marker of cellular hypertrophy, the matrix metalloproteinases (MMP), MMP-13 and MMP-9, as well as the transcriptional factors, Sox9 and Cbfa1, the growth factors basic fibroblast growth factor (bFGF), parathyroid hormone-related peptide (PTHrP), transforming growth factor (TGF)beta1, and beta2, Indian hedgehog (Ihh), and the matrix protein osteocalcin. These were analyzed in relationship to cell division defined by cyclin B2 expression. Two peaks of gene expression activity were observed. One was transient, limited, and located immediately before and at the onset of cyclin B2 expression in the early proliferative zone. The other was generally much more pronounced and was located in the early hypertrophic zone. The upregulation of expression of COL2A1, its transcriptional activator Sox9, osteocalcin, MMP-13, and TGFbeta2 was observed immediately before and at the onset of cyclin B2 expression and also in the hypertrophic zones. The upregulation of COL10A1, Cbfa1, MMP-9, TGFbeta-1, and Ihh gene expression was associated exclusively with the terminal differentiation of chondrocytes at the time of mineral formation in the extracellular matrix. In contrast, bFGF and PTHrP expression was observed in association with the onset of cyclin B2 expression and hypertrophy. This initial cluster of gene expression associated predominantly with matrix assembly and onset of cell proliferation is therefore characterized by expression of regulatory molecules distinct from those involved at hypertrophy. Together these results identify separate phases of coordinated gene expression associated with the development of the physis in endochondral bone formation.
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PMID:Distinct phases of coordinated early and late gene expression in growth plate chondrocytes in relationship to cell proliferation, matrix assembly, remodeling, and cell differentiation. 1273 23

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. The C(2)H(2) zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes and are important for human heart development and diseases. Here we have identified and characterized a novel zinc-finger gene named ZNF322 using degenerated primers from a human embryo heart cDNA library. The gene contains four exons and spans 23.2kb in chromosome 6p22.1 region, and transcribes a 2.7kb mRNA that encodes a protein with 402 amino acid residues. The predicted protein contains 9 tandem C(2)H(2)-type zinc-finger motifs. Northern blot analysis shows that ZNF322 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells, ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter gene assays show that ZNF322 is a transcriptional activator. Furthermore, overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways.
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PMID:ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. 1555 80

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a small secreted matrix protein expressed in developing and adult cartilage and by chondrocytes in culture. We have previously shown that the expression of Cd-rap, like many other cartilage matrix proteins, is repressed by interleukin 1beta and that the transcription factor CCAAT/enhancer-binding protein (C/EBP) beta plays an important role in the interleukin 1beta-induced repression (Okazaki, K., Li, J., Yu, H., Fukui, N., and Sandell, L. J. (2002) J. Biol. Chem. 277, 31526-31533). The co-activators CREB-binding protein (CBP) and p300 are transcriptional co-regulators that participate in the activities of many different transcription factors including C/EBP. Here we show that CBP/p300 can reverse the inhibitory effect of C/EBP and moreover can stimulate expression of Cd-rap. The mechanism of this effect is shown to involve a unique synergy whereby CBP/p300 stimulate Cd-rap gene expression by at least two mechanisms. First, binding of CBP/p300 to C/EBPbeta leads to sequestration of C/EBP eliminating DNA binding and subsequent repression; second, binding of CBP/p300 to the transcriptional activator Sox9 increases Sox9 DNA binding to the Cd-rap promoter leading to further stimulation of gene transcription. This is an example of a complementary transcriptional network whereby two very different mechanisms act together to confer a functional increase in transcription. This new paradigm is likely generally applicable to cartilage genes as Col2a1 cartilage collagen gene responds similarly.
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PMID:Transcriptional Co-activators CREB-binding protein/p300 increase chondrocyte Cd-rap gene expression by multiple mechanisms including sequestration of the repressor CCAAT/enhancer-binding protein. 1572 56