Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis by means of two-dimensional (2D) gel electrophoresis of the protein patterns of normal and psoriatic unfractionated non-cultured keratinocytes has revealed a few low-molecular-weight proteins that are highly up-regulated in psoriatic skin. These include psoriasin; calgranulin B, also known as MRP 14, L1, or calprotectin; calgranulin A or MRP 8; and cystatin A or stefin A. Here, we have cloned and sequenced the cDNA (clone 1592) encoding a new member of this group of low-molecular-weight proteins [isoelectric focusing (IEF) SSP 3007 in the keratinocyte 2D gel protein database] that we have termed PA-FABP (psoriasis-associated fatty acid-binding protein). The deduced sequence predicted a protein with molecular weight of 15,164 daltons and a calculated pI of 6.96, values that are close to those recorded in the keratinocyte 2D gel protein database. The protein comigrated with PA-FABP as determined by 2D gel analysis of [35S]-methionine-labeled proteins expressed by transformed human amnion (AMA) cells transfected with clone 1592 using the vaccinia virus expression system and reacted with a rabbit polyclonal antibody raised against 2D gel purified PA-FABP. Structural analysis of the amino acid sequence revealed 48%, 52%, and 56% identity to known low-molecular-weight fatty acid-binding proteins belonging to the FABP family. Northern blot analysis showed that PA-FABP mRNA is indeed highly up-regulated in psoriatic keratinocytes. The transcript is present in human cell lines of epithelial and lymphoid (Molt 4) origin but cannot be detected in normal or SV40 transformed MRC-5 fibroblasts. 2D gel protein analysis of normal primary keratinocytes cultured for at least 8 d under conditions that promoted incomplete terminal differentiation [serum-free keratinocyte (SFK) medium supplemented with epidermal growth factor (EGF), pituitary extract, and 10% fetal calf serum] revealed a strong up-regulation of PA-FABP, psoriasin, calgranulins A and B, and a few other proteins that are highly expressed in psoriatic skin. The levels of these proteins exceeded by far those observed in non-cultured normal keratinocytes implying that the cultured cells have followed an altered pattern of differentiation that resembles--at least in part--that of non-cultured psoriatic keratinocytes. The implications of these results for the study of psoriasis are discussed.
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PMID:Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. 151 66

SMAD proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor beta (TGFbeta) superfamily of growth factors. Certain SMAD proteins (Smad1, 2, 3, and 5) can act as regulated transcriptional activators. This process involves phosphorylation of these proteins by activated TGFbeta receptors. Recently, Smad6 and Smad7 were identified; they antagonize TGFbeta signaling by preventing the activation of signal-transducing SMAD complexes. TGFbeta rapidly induces the expression of Smad7 mRNA, suggesting participation of Smad7 in a negative feedback loop to control TGFbeta responses. Similarly, epidermal growth factor (EGF) and interferon gamma (IFN-gamma) have been reported to induce Smad7 expression. In a rat model system of liver fibrosis, TGFbeta inducibility of Smad7 is abrogated during transformation of hepatic stellate cells (HSC), indicating an important switch in transcriptional regulation of the gene. With the detailed characterization of the rat Smad7 genomic organization including the promoter region, we present the first identified Smad7 gene so far. The gene is composed of four exons separated by three introns covering a DNA region of about 30 kilobases (kb) in total. The major transcription start site is conserved between rat and mouse, and two polyadenylation signals were detected. In the promoter region, a potential CAGA box, a signal transducer and activator of transcription (STAT) factor-related recognition site, and different AP1 sites were identified, which could be the targets of TGFbeta, IFN-gamma, and EGF-dependent Smad7 transcription initiation.
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PMID:Genomic locus and promoter region of rat Smad7, an important antagonist of TGFbeta signaling. 1065 34

In order to understand the mechanisms underlying the development of resistance to a pure antiestrogen we established three human breast carcinoma cell lines resistant to ZM 182780 (ZM) (Faslodex). Long-term cultivation of the ERalpha-positive, 17beta-estradiol (E(2))-responsive cell lines T47D, ZR-75-1, and MCF-7 with the pure antiestrogen ZM 182780 resulted in the T47D-r, ZR-75-1-r, and MCF-7-r cell lines, which proliferate continuously in the presence of 10(-6)M ZM 182780. The resulting antiestrogen-resistant cells grow equally well in medium with or without E(2) and in medium with or without ZM 182780 indicating that they are no longer estrogen-responsive. ERalpha expression was lost at the protein level in all three resistant cell lines. At the mRNA level, the ERalpha was only faintly detectable in T47D-r, whereas a weak signal was seen in ZR-75-1-r and MCF-7-r. By reverse transcription-polymerase chain reaction (RT-PCR) the ERbeta was detectable in the antiestrogen-sensitive and -resistant breast cancer cell lines, however, ZR75-1-r contained the smallest signal for ERbeta. In all three antiestrogen-resistant cells the PR was undetectable, whereas binding of epidermal growth factor (EGF) and protein expression of epidermal growth factor receptor (EGFR) were increased. To analyse alterations in the gene expression pattern in more detail Atlas arrays were hybridised with RNA isolated from T47D-r and T47D and the two Ca2+-binding proteins calgranulin A and B were found to be up-regulated in T47D-r compared to T47D. Calgranulin A and B were also both up-regulated in ZR-75-1-r and MCF-7-r compared to their antiestrogen-sensitive counterparts. Loss of ERalpha expression may be linked to the acquisition of antiestrogen resistance and enhanced expression of the EGFR and of proteins of the S100 family of Ca2+-binding proteins which may contribute to the outgrowth of resistant cells.
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PMID:Studies on the development of resistance to the pure antiestrogen Faslodex in three human breast cancer cell lines. 1279 55