Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86WD7 (GCET1)
 18 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Centerin [SERPINA9/GCET1 (germinal centre B-cell-expressed transcript 1)] is a serpin (serine protease inhibitor) whose expression is restricted to germinal centre B-cells and lymphoid malignancies with germinal centre B-cell maturation. Expression of centerin, together with bcl-6 and GCET2, constitutes a germinal centre B-cell signature, which is associated with a good prognosis in diffuse large B-cell lymphomas, but the molecular basis for this remains to be elucidated. We report here the cloning, expression and molecular characterization of bacterial recombinant centerin. Biophysical studies demonstrated that centerin was able to undergo the 'stressed to relaxed' conformational change which is an absolute requirement for protease inhibitory activity. Kinetic analysis showed that centerin rapidly inhibited the serine protease trypsin (k(a)=1.9x10(5) M(-1) x s(-1)) and also demonstrated measurable inhibition of thrombin (k(a)=1.17x10(3) M(-1) x s(-1)) and plasmin (k(a)=1.92x10(3) M(-1) x s(-1)). Centerin also bound DNA and unfractionated heparin, although there was no functionally significant impact on the rate of inhibition. These results suggest that centerin is likely to function in vivo in the germinal centre as an efficient inhibitor of a trypsin-like protease.
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PMID:Molecular characterization of centerin, a germinal centre cell serpin. 1744 96

GCET1 (germinal center B cell-expressed transcript-1) gene codes for a serpin expressed in germinal center (GC) B cells. Following the observation that follicular lymphoma cases exhibit an increased level of Gcet1 expression, compared with follicular hyperplasia, we have characterized Gcet1 protein expression in human tissues, cell lines, and a large series of lymphomas. To this end, we have performed immunohistochemical and Western blot analyses using a newly generated monoclonal antibody that is reactive in paraffin-embedded tissues. Our results demonstrate that Gcet1 is expressed exclusively by neoplasms hypothetically to be arrested at the GC stage of differentiation, including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a subset of diffuse large B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, and Burkitt lymphoma. Within these tumors, Gcet-1 protein expression is restricted to a subset of GC B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic GC B cells. None of the other B-cell lymphomas, that is, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and mantle cell lymphoma, was Gcet1(+), which underlines the potential utility of Gcet1 expression in lymphoma diagnosis. The results of RNA and protein expression should prompt further investigation into the role of Gcet1 in regulating B-cell survival.
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PMID:Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas. 1789 15

Centerin (SERPINA9/GCET1) is a protease inhibitor with expression restricted to germinal center B cells and lymphoid malignancies with germinal center B-cell maturation. Expression of the centerin gene transcript, along with bcl-6 and GCET2/HGAL, constitutes a molecular signature associated with a good prognosis in diffuse large B-cell lymphomas. A monoclonal antibody to centerin was generated and used for Western blotting, immunohistochemistry, and immunofluorescence. Centerin expression was demonstrated in Burkitt lymphoma Raji cells. An immunohistochemical survey of normal tissues showed centerin expression in germinal center B cells in lymphoid follicles in tonsil, lymph node, and lymphoid tissue in the gastrointestinal tract. Centerin was strongly expressed in most follicular lymphomas. In addition, 14 (47%) of 30 diffuse large B-cell lymphomas were positive for centerin, which correlated most closely with CD10 expression. Immunohistochemical expression of centerin further defines the germinal center cell origin of a subgroup of lymphomas.
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PMID:Expression of the serpin centerin defines a germinal center phenotype in B-cell lymphomas. 1855 Apr 80

Implementation of new phenotypic markers in routine diagnostics of hematolymphoid neoplasms is a challenging task with a plethora of potentially relevant proteins. We investigated 3 recently discovered proteins expressed in the germinal centers of lymph nodes (LMO2, GCET1, and HGAL) in a compilation of leukemia, lymphoma, and thymic tumor entities. Altogether, 1590 cases (1519 on tissue microarrays, 71 on conventional slides) were included. Expressions of LMO2, GCET1, and HGAL were investigated by immunohistochemistry, evaluated for their differential diagnostic relevance, and correlated with the clinical outcome of patients. In Hodgkin lymphoma (HL), the expression of LMO2, GCET1, and HGAL could be largely seen in tumor cells of nodular lymphocyte predominant HL (NLPHL) but only occasionally in classic HL. The majority of B-cell lymphoma cases was positive for LMO2 [except for Burkitt lymphoma (BL)] and HGAL with weaker to moderate staining intensity, compared with the intensely staining follicular lymphomas (FL). Except for FL (60% of cases) and diffuse large B-cell lymphomas (DLBCL, 36% of cases), all other B-cell lymphomas expressed little or no GCET1. In thymomas, the non-neoplastic immature T-cells were LMO2-negative, whereas the neoplastic lymphoblasts were LMO2-positive in more than half of the lymphoblastic lymphomas (LBL). Our findings provide new potential assistance in the differential diagnosis of FL to marginal zone lymphoma, classic HL to NLPHL and primary mediastinal B-cell lymphoma, DLBCL to BL, and thymoma to LBL. Finally, HGAL proved to be a prognostic marker for classic HL regarding the background population and in DLBCL regarding the tumor cells.
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PMID:Diagnostic Utility of the Germinal Center-associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms. 2520 28