Biomedical subjects

Sirle Laos

Publications and source records attributed to Sirle Laos.

5 recordsLinked to original sources

PubMed2006

Inhibition of NF-kappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells.

CD43 is a heavily O-glycosylated type I trans-membrane protein, expressed at high levels on the surface of leukocytes. It is frequently overexpressed in early colon adenomas, but not in normal colon epithelial cells. To identify CD43 target genes, gene array analysis was performed using a tetracycline-inducible CD43 expression system in human colon adenocarcinoma SW480 cells. CD43 was demonstrated to down-regulate a variety of chemokine genes. Overexpression of CD43 suppressed constitutive as well as PMA-induced NF-kappaB activation and reduced the DNA binding of transcription factor p65 but not p50. Furthermore, a reduced NF-kappaB responsive promoter activity was observed and a decreased expression of proinflammatory chemokines MCP-1, IL-8 and GRO-alpha. These results suggest that overexpression of CD43 suppresses a subset of NF-kappaB target genes, partly via the inhibition of p65 transcriptional activity.

Active Transport, Cell Nucleus↗

PubMed2005

Shedding and gamma-secretase-mediated intramembrane proteolysis of the mucin-type molecule CD43.

CD43 is a transmembrane molecule that contains a 123-aminoacids-long cytoplasmic tail and a highly O-glycosylated extracellular domain of mucin type. Endogenous CD43 expressed in COLO 205, K562 and Jurkat cells revealed a membrane-associated, 20 kDa CD43-specific cytoplasmic tail fragment (CD43-CTF) upon inhibition of gamma-secretase. This fragment was formed by an extracellular cleavage, as it was not accumulated after treating cells with 1,10-phenanthroline, a metalloprotease inhibitor. When CD43 was transfected into HEK-293 cells expressing dominant-negative PS1 (presenilin-1), the CD43-CTF was accumulated, but not in cells with wild-type PS1. Owing to its accumulation in the presence of a non-functional PS variant, it may thus be a novel gamma-secretase substrate. This CTF is formed by an extracellular cleavage close to the membrane, is a fragment that can be concluded to be a substrate for gamma-secretase. However, the intracellular gamma-secretase product has not been possible to detect, suggesting a quick processing of this product. During normal growth the CTF was not found without gamma-secretase inhibition, but when the cells (COLO 205) were very confluent the fragment could be detected. The intracellular domain of CD43 has previously been shown to contain a functional nuclear localization signal, and has been suggested to be involved in gene activation. From this and the present results, a novel way to explain how mucin-type molecules may transduce intracellular signals can be proposed.

Amyloid Precursor Protein Secretases↗

PubMed2004

Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian, and Altaian populations. In addition to the seven previously specified subhaplogroups, we define fifteen novel subclades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1*, H1b, H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct phylogeographic patterns. The monophyletic subhaplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

Asia↗

PubMed2004

Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF.

CD43 or leukosialin is a transmembrane sialoglycoprotein, whose extracellular domain participates in cell adhesiveness and the cytoplasmic tail regulates a variety of intracellular signal transduction pathways involved in cell proliferation. CD43 is abundantly expressed on the surface of hematopoietic cells, but CD43 expression is also frequently found in the tumor cells of nonhematopoietic origin. In the early stages of some tumors, the accumulation of tumor suppressor protein p53 has been described. Here, we show that the expression of CD43 causes the induction of functionally active p53 protein. Moreover, we found that the activation of p53 by CD43 is mediated by tumor suppressor protein ARF. The coexpression of CD43 and ARF in ARF-null mouse embryonic fibroblasts resulted in programmed cell death, but that was not the case when CD43 alone was expressed in these cells. These data provide the first evidence of the connection between p53- and CD43-dependent pathways.

ADP-Ribosylation Factor 1↗

PubMed2004

CD43 has a functional NLS, interacts with beta-catenin, and affects gene expression.

CD43 is a transmembrane molecule with a highly O-glycosylated extracellular domain of mucin type. It is a normal constituent of leukocytes and found in colon adenoma, but not in normal colon epithelia. Here it is shown that the cytoplasmic tail of CD43 contains a functional bipartite nuclear localization signal directing it to the nucleus. The intracellular domain of CD43 interacts with beta-catenin and causes an upregulation of the beta-catenin target genes c-MYC and CyclinD1. The present results suggest that CD43 can be involved in nuclear signaling and via beta-catenin interaction be involved in cell proliferation.

Amino Acid Sequence↗