TRB2交互作用蛋白之功能研究
Functional characterization of TRB2 interacting proteins
Date Issued
2007
Date
2007
Author(s)
Hung, Chien-Min
DOI
en-US
Abstract
Tribbles, a serine/threoine protein kinase family member, has been shown to coordinate cell proliferation, migration and morphogenesis during the development of Drosophila embryo. Although Tribbles are highly conserved throughout the evolution, the physiological function of mammalian orthologs is largely unknown. Recently, our laboratory has demonstrated that human Tribbles ortholog 2 (TRB2) is involved in GM-CSF withdrawal-induced apoptosis of TF-1 cells, a human erytholeukemia cell line. TRB2 mRNA is highly induced upon removal of GM-CSF, and ectopic expression of TRB2 promotes apoptosis of cells mainly of the hematopoietic origin. However, the underlying mechanism of TRB2-induced apoptosis needs to be further elucidated. For this purpose, we firstly report here that the putative kinase activity is not required for the pro-apoptotic function of TRB2, and its protein level is regulated through the proteasome-
dependent pathway. Second, a yeast two-hybrid screen was previously applied and several candidate genes were identified. In this dissertation, we further characterized the interactions of three of these proteins, MNK2b, γ-Parvin and UBC9, with TRB2 in vitro and in mammalian cells. The interaction of TRB2 with MNK2b or γ-Parvin could be demonstrated in GST pull-down experiments. The co-immunoprecipiation and the mammalian two-hybrid assay were further used to confirm TRB2 associates with γ-Parvin in cells. In contrast, the interaction between TRB2 and UBC9 was not detected both in vitro and in vivo. Last, we explored the biological effect of these interactions on apoptosis and found that MNK2b and γ-Parvin partially interfere with the pro-apoptotic function of TRB2. Taken together, our data suggest that γ-Parvin is likely a physiological binding protein of TRB2 and may play a role in TRB2-induced apoptosis.
Subjects
細胞凋亡
細胞激素剝奪
Tribbles
MNK2b
γ-Parvin
UBC9
Apoptosis
Cytokine deprivation
Type
other
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