Overexpression of TDP-43 causes partially p53-dependent G2/M arrest and p53-independent cell death in HeLa cells

Kikyo Lee, Hiroaki Suzuki, Sadakazu Aiso, Masaaki Matsuoka

研究成果: Article

5 引用 (Scopus)

抄録

It has been hypothesized that the dysregulation of transactive response DNA-binding protein-43 (TDP-43) in neurons is closely linked to the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions. However, it remains undefined whether the dysregulation of TDP-43 in non-neuronal cells, such as glial cells, contributes to the pathogenesis of these neurodegenerative diseases. Primarily using HeLa cells, we show that a low-grade overexpression of TDP-43, 2- to 5-fold greater than endogenous expression, which is thought to mimic the gain of function of TDP-43, induced cell cycle arrest at the G2/M phase and cell death in cultured non-neuronal cells. Since the activation of p53 may induce G2/M arrest and/or cell death in many abnormal situations, we examined the mechanism underlying G2/M arrest from the standpoint of p53 regulation. It was determined that the TDP-43-induced G2/M arrest was attenuated, while TDP-43-induced death was not attenuated, in cells in which the p53 function was compromised. These data collectively indicate that TDP-43 causes G2/M arrest in a partially p53-dependent manner and it causes cell death in a p53-independent manner in cycling cells. Because it is likely that the impaired proliferation in glial cells causes a decrease in the neuron-supporting ability, these findings further suggests that the gain of function of TDP-43 may cause neurotoxicity by inducing cell cycle arrest and death in glial cells.

元の言語English
ページ(範囲)271-276
ページ数6
ジャーナルNeuroscience Letters
506
発行部数2
DOI
出版物ステータスPublished - 2012 1 11

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DNA-Binding Proteins
HeLa Cells
Cell Death
Neuroglia
Cell Cycle Checkpoints
Frontotemporal Lobar Degeneration
Neurons
Aptitude
G2 Phase
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Cell Division
Cause of Death

ASJC Scopus subject areas

  • Neuroscience(all)

これを引用

Overexpression of TDP-43 causes partially p53-dependent G2/M arrest and p53-independent cell death in HeLa cells. / Lee, Kikyo; Suzuki, Hiroaki; Aiso, Sadakazu; Matsuoka, Masaaki.

:: Neuroscience Letters, 巻 506, 番号 2, 11.01.2012, p. 271-276.

研究成果: Article

Lee, Kikyo ; Suzuki, Hiroaki ; Aiso, Sadakazu ; Matsuoka, Masaaki. / Overexpression of TDP-43 causes partially p53-dependent G2/M arrest and p53-independent cell death in HeLa cells. :: Neuroscience Letters. 2012 ; 巻 506, 番号 2. pp. 271-276.
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