scholarly journals GNL3L stabilizes the TRF1 complex and promotes mitotic transition

2009 ◽  
Vol 185 (5) ◽  
pp. 827-839 ◽  
Author(s):  
Qubo Zhu ◽  
Lingjun Meng ◽  
Joseph K. Hsu ◽  
Tao Lin ◽  
Jun Teishima ◽  
...  
Keyword(s):  
Binding Protein ◽  
Cell Cycle Control ◽  
Order Structure ◽  
Guanine Nucleotide Binding Protein ◽  
Interacting Protein ◽  
Growth Defects ◽  
Binding Factor ◽  
Guanine Nucleotide Binding ◽  
Telomeric Association

Telomeric repeat binding factor 1 (TRF1) is a component of the multiprotein complex “shelterin,” which organizes the telomere into a high-order structure. TRF1 knockout embryos suffer from severe growth defects without apparent telomere dysfunction, suggesting an obligatory role for TRF1 in cell cycle control. To date, the mechanism regulating the mitotic increase in TRF1 protein expression and its function in mitosis remains unclear. Here, we identify guanine nucleotide-binding protein-like 3 (GNL3L), a GTP-binding protein most similar to nucleostemin, as a novel TRF1-interacting protein in vivo. GNL3L binds TRF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TRF1, preventing promyelocytic leukemia body recruitment of telomere-bound TRF1, and stabilizing TRF1 protein by inhibiting its ubiquitylation and binding to FBX4, an E3 ubiquitin ligase for TRF1. Most importantly, the TRF1 protein-stabilizing activity of GNL3L mediates the mitotic increase of TRF1 protein and promotes the metaphase-to-anaphase transition. This work reveals novel aspects of TRF1 modulation by GNL3L.

scholarly journals Gαi1and Gαi3regulate macrophage polarization by forming a complex containing CD14 and Gab1

2015 ◽  
Vol 112 (15) ◽  
pp. 4731-4736 ◽  
Author(s):  
Xianjing Li ◽  
Duowei Wang ◽  
Zhen Chen ◽  
Ermei Lu ◽  
Zhuo Wang ◽  
...  
Keyword(s):  
Binding Protein ◽  
Macrophage Polarization ◽  
Growth Factor Receptor ◽  
Guanine Nucleotide Binding Protein ◽  
Akt Activation ◽  
Proteasome Pathway ◽  
Guanine Nucleotide Binding ◽  
Underlying Mechanisms

Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3knockdown in bone marrow-derived macrophage cells (Gαi1/3KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincided with decreased Akt activation. Further, Gαi1/3deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.

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