| 1. |
- Andersson, Christian X, 1973, et al.
(författare)
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CD43 has a functional NLS, interacts with beta-catenin, and affects gene expression
- 2004
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Ingår i: Biochem. Biophys. Res. Commun.. - : Elsevier BV. ; 316:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Andersson, Christian X, 1973, et al.
(författare)
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Shedding and gamma-Secretase mediated intramembrane proteolysis of the mucin-type molecule CD43
- 2005
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Ingår i: Biochem J.. ; 387:2, s. 377-384
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Fernandez-Rodriguez, Julia, 1965, et al.
(författare)
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The leukocyte antigen CD43 is expressed in different cell lines of nonhematopoietic origin.
- 2002
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - 1010-4283. ; 23:4, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- CD43 is an abundant transmembrane sialoglycoprotein in leukocyte-type cell lines, but it has also been suggested to be present in colon adenomas and colon carcinomas. We have now shown that CD43 is expressed in a variety of cell lines of different origins (CaSKI, A549, 293, MTSV1-7, MCF7, HT-1080, Jurkat, K562, COLO 205, HT-29, Caco-2, DLD-1 and SW480). The level of expression of CD43 mRNA was analyzed by reverse transcriptase-polymerase chain reaction and that of the protein by immunoprecipitation and Western blot, flow cytometry and confocal microscopy using two monoclonal anti-CD43 antibodies (L10 and 4D2). As all cell lines expressed CD43, it is suggested that CD43 has a more fundamental function than previously believed and thus cannot be considered only as a specific leukocyte marker.
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| 4. |
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| 5. |
- Kadaja-Saarepuu, L, et al.
(författare)
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CD43 promotes cell growth and helps to evade FAS-mediated apoptosis in non-hematopoietic cancer cells lacking the tumor suppressors p53 or ARF.
- 2008
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 27:12, s. 1705-15
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Tidskriftsartikel (refereegranskat)abstract
- CD43 is a highly glycosylated transmembrane protein expressed on the surface of most hematopoietic cells. Expression of CD43 has also been demonstrated in many human tumor tissues, including colon adenomas and carcinomas, but not in normal colon epithelium. The potential contribution of CD43 to tumor development is still not understood. Here, we show that overexpression of CD43 increases cell growth and colony formation in mouse and human cells lacking expression of either p53 or ARF (alternative reading frame) tumor-suppressor proteins. In addition, CD43 overexpression also lowers the detection of the FAS death receptor on the cell surface of human cancer cells, and thereby helps to evade FAS-mediated apoptosis. However, when both p53 and ARF proteins are present, CD43 overexpression activates p53 and suppresses colony formation due to induction of apoptosis. These observations suggest CD43 as a potential contributor to tumor development and the functional ARF-p53 pathway is required for the elimination of cells with aberrant CD43 expression.
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| 6. |
- Laos, Sirle, 1976, et al.
(författare)
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Inhibition of NF-kappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells.
- 2006
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Ingår i: International journal of oncology. - 1019-6439. ; 28:3, s. 695-704
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Laos, Sirle, 1976
(författare)
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Tumor biological aspects of the mucin-like glycoprotein CD43
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer cells overexpress aberrant forms and amounts of mucins, which contribute to tumor development by regulating cell growth, survival, adhesion, invasion and immune responses. CD43, a type I transmembrane protein, is a mucin-like molecule expressed under normal physiological conditions by most hematopoietic cell types. CD43 is also frequently expressed in early stages of colorectal adenomas, but not in normal colon epithelial cells. The role of CD43 in colon tumor cells is unknown. The purpose of the present study was to investigate the expression and function of CD43 in tumor cells and evaluate the potential role of CD43 in colon tumor development.We have studied CD43 expression at both mRNA and protein levels by RT-PCR, flow cytometry, western blot and immunohistochemistry in tumor cell lines of different tissue origin. CD43 was found ubiquitously expressed in all studied cell lines, although with various expression levels and glycoforms. CD43 expression was shown in the colon adenocarcinoma cell lines COLO 205, Caco-2, SW 480, HT-29 and DLD-1.The proteolytic processing of type I transmembrane proteins by the ×-secretase complex is an important mechanism for their functional regulation. Previous results of our group suggested that the cytoplasmic tail of CD43 could localize to the cell nucleus and act as a signaling molecule. This could be linked to our observation that CD43 is a substrate for g-secretase that releases the intracellular part of CD43 into the cytosol.To study the function of CD43 in colon tumors, we increased the CD43 protein level by transient transfections or by using a tetracycline-regulated expression system. In the SW 480 cell line, CD43 overexpression inhibited nuclear localization of the transcription factor NF-kappaB p65 and suppressed expression of the chemokines MCP-1, IL-8 and GRO-alpha. It is known that activated tumor suppressors, such as p53 and ARF, inhibit the transcriptional activity of NF-kappaB. In fact, overexpression of CD43 activated p53 when ARF was present and resulted in cell death. However, CD43 overexpression promoted colony formation, cell growth and cell survival in the cells lacking either expression of ARF or p53. Moreover, high expression of CD43 helped cells to evade Fas-mediated apoptosis. This provides the first indication that expression of CD43 in a certain cellular context enhances a transformed phenotype of the cell.In summary, the results give new insights in the abnormal expression and function of CD43. This thesis suggests that CD43 expression by tumor cells may contribute to immune surveillance, cell growth, cell survival, and evasion of apoptosis.
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