Biomedical subjects

Like Qu

Publications and source records attributed to Like Qu.

5 recordsLinked to original sources

PubMed2006

CIAP2 inhibits anigen receptor signaling by targeting Bcl10 for degredation.

The cellular inhibitor of apoptosis 2 (cIAP2) is a RING-containing protein ubiquitin ligase. In a high percentage of mucosa-associated lymphoid tissue (MALT) lymphomas, cIAP2 is fused to MALT1/paracaspase as a result of the t(11;18)(q21;q21) translocation. The physiological function of cIAP2 in lymphocytes and how this function may be affected by the translocation are not well understood. We have shown that cIAP2 normally inhibits antigen receptor signaling by mediating the ubiquitination and degradation of Bcl10, a critical component for antigenic signaling to NF-kappaB. The cIAP2-MALT1 fusion protein lacks this E3 activity and is incapable of ubiquitinating Bcl10, likely causing enhanced Bcl10 expression. Furthermore, cIAP2-MALT1 and Bcl10 synergistically activate NF-kappaB. These results reveal a physiological function of cIAP2, identify Bcl10 upregulation as a unifying molecular mechanism for MALT lymphomas, and define the mechanism and effects of this upregulation in t(11;18)-positive MALT lymphomas.

Adaptor Proteins, Signal Transducing↗

PubMed2006

cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas.

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-kappaB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-kappaB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

Caspases↗

PubMed2004

Control of tumor suppressor p53 function by endoplasmic reticulum stress.

Alterations in the homeostasis of the endoplasmic reticulum (ER) by various forms of stress can lead to the accumulation of unfolded proteins and protein aggregates that are detrimental to cell survival. Eukaryotic cells can adapt to ER stress by activating specific signaling pathways and mechanisms, whose primary purpose is to limit the accumulation of unfolded proteins in the ER. We recently reported a novel mechanism of cell adaptation to ER stress, which proceeds through the inhibition of the apoptotic function of the tumor suppressor p53 (Genes Dev 2004;18:261-277). We found that ER stress increases the cytoplasmic localization and enhances the destabilization of the tumor suppressor. This process requires the phosphorylation of p53 at serine 315 and serine 376, which is mediated by the activation of glycogen synthase kinase-3beta (GSK-3beta). ER stress also prevents p53 activation and p53-mediated apoptosis in response to DNA damage. These findings demonstrate that ER stress utilizes mechanisms that are distinct from other types of stress to modulate p53. In addition, they reveal that ER stress and nuclear DNA damage can induce inter-organellar cross-talk pathways targeting p53 with important implications for the treatment of tumors with dysfunctional ER.

Cell Line, Tumor↗

PubMed2003

A possible receptor for beta 2 glycoprotein I on the membrane of hepatoma cell line smmc7721.

OBJECTIVES: To study the interaction of beta-2-glycoprotein I (beta 2GPI) with the membrane of hepatocytes and determine whether beta 2GPI participates in HBV infection. METHODS: Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter (FACS) analysis were used to detect the specific interaction of beta 2GPI with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60. RESULTS: A specific 40 kDa beta 2GPI band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC-beta 2GPI to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC-beta 2GPI to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells (P < 0.01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-beta 2GPI. CONCLUSIONS: There is a specific beta 2GPI-binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the beta 2GPI receptor may participate in HBV infection of hepatocytes.

Animals↗

PubMed2002

[Relation between Beta-2-glycoprotein I and hepatitis B virus surface antigen].

OBJECTIVE: To clarify the binding character between Beta-2-glycoprotein I (Beta-2-GPI) and HBsAg. METHODS: Beta-2-GPI was purified from human plasma and labelled with biotin. Solid phase enzyme linked absorbance assay was used to investigate its binding with HBsAg. RESULTS: Biotinylated Beta-2-GPI was found to bind HBsAg and the reaction could be inhibited by excess unlabelled Beta-2-GPI. CONCLUSIONS: Beta-2-GPI may play a role in hepatitis B virus infection.

Binding Sites↗