scholarly journals Competitive Nuclear Export of Cyclin D1 and Hic-5 Regulates Anchorage Dependence of Cell Growth and Survival

2009 ◽  
Vol 20 (1) ◽  
pp. 218-232 ◽  
Author(s):  
Kazunori Mori ◽  
Etsuko Hirao ◽  
Yosuke Toya ◽  
Yukiko Oshima ◽  
Fumihiro Ishikawa ◽  
...  

Anchorage dependence of cell growth and survival is a critical trait that distinguishes nontransformed cells from transformed cells. We demonstrate that anchorage dependence is determined by anchorage-dependent nuclear retention of cyclin D1, which is regulated by the focal adhesion protein, Hic-5, whose CRM1-dependent nuclear export counteracts that of cyclin D1. An adaptor protein, PINCH, interacts with cyclin D1 and Hic-5 and potentially serves as an interface for the competition between cyclin D1 and Hic-5 for CRM1. In nonadherent cells, the nuclear export of Hic-5, which is redox-sensitive, was interrupted due to elevated production of reactive oxygen species, and cyclin D1 was exported from the nucleus. When an Hic-5 mutant that was continuously exported in a reactive oxygen species-insensitive manner was introduced into the cells, cyclin D1 was retained in the nucleus under nonadherent conditions, and a significant population of cells escaped from growth arrest or apoptosis. Interestingly, activated ras achieved predominant cyclin D1 nuclear localization and thus, growth in nonadherent cells. We report a failsafe system for anchorage dependence of cell growth and survival.

2016 ◽  
Vol 12 (5) ◽  
pp. 3537-3542 ◽  
Author(s):  
Chaofeng Li ◽  
Weichao Peng ◽  
Xin Song ◽  
Qian Wang ◽  
Wenyue Wang

Nature ◽  
2003 ◽  
Vol 422 (6930) ◽  
pp. 442-446 ◽  
Author(s):  
Julia Foreman ◽  
Vadim Demidchik ◽  
John H. F. Bothwell ◽  
Panagiota Mylona ◽  
Henk Miedema ◽  
...  

2017 ◽  
Vol 182 (4) ◽  
pp. 1663-1674 ◽  
Author(s):  
Sung-Jo Kim ◽  
Eunmi Hwang ◽  
Sun Shin Yi ◽  
Ki Duk Song ◽  
Hak-Kyo Lee ◽  
...  

2016 ◽  
Vol 8 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Sanjeev Choudhary ◽  
Istvan Boldogh ◽  
Allan R. Brasier

The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperates in the IIR. We discuss recent discoveries about 2 nuclear ROS signaling pathways controlling innate immunity. Nuclear ROS oxidize guanine bases to produce mutagenic 8-oxoguanine, a lesion excised by 8-oxoguanine DNA glycosylase1/AP-lyase (OGG1). OGG1 forms a complex with the excised base, inducing its nuclear export. The cytoplasmic OGG1:8-oxoG complex functions as a guanine nucleotide exchange factor, triggering small GTPase signaling and activating phosphorylation of the nuclear factor (NF)κB/RelA transcription factor to induce immediate early gene expression. In parallel, nuclear ROS are detected by ataxia telangiectasia mutated (ATM), a PI3 kinase activated by ROS, triggering its nuclear export. ATM forms a scaffold with ribosomal S6 kinases, inducing RelA phosphorylation and resulting in transcription-coupled synthesis of type I and type III interferons and CC and CXC chemokines. We propose that ATM and OGG1 are endogenous nuclear ROS sensors that transmit nuclear signals that coordinate with outside-in pattern recognition receptor signaling, regulating the IIR.


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