PUMA Overexpression Induces Reactive Oxygen Species Generation and Proteasome-Mediated Stathmin Degradation in Colorectal Cancer Cells
-
- Zhihe Liu
- 1Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine and
-
- Huimei Lu
- 1Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine and
-
- Honglian Shi
- 2The EPR Center and Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, New Mexico;
-
- Yuchun Du
- 3Biosciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico; and
-
- Jian Yu
- 4Department of Pathology, Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
-
- Sheng Gu
- 3Biosciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico; and
-
- Xian Chen
- 3Biosciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico; and
-
- Ke Jian Liu
- 2The EPR Center and Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, New Mexico;
-
- Chien-an A. Hu
- 1Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine and
抄録
<jats:title>Abstract</jats:title> <jats:p>Increased amounts of reactive oxygen species (ROS) induce apoptosis in mammalian cells. PUMA (P53 up-regulated modulator of apoptosis), a mitochondrial proapoptotic BH3-only protein, induces rapid apoptosis through a Bax- and mitochondria-dependent pathway. However, the molecular basis of PUMA-induced apoptosis is largely not understood. Using a combination of biophysical and biochemical methods and PUMA-inducible colorectal cells, DLD-1.PUMA, we showed that (a) PUMA-induced apoptosis is dose and time dependent; (b) PUMA-induced apoptosis is directly associated with ROS generation; (c) diphenyleneiodonium chloride, a ROS blocker, or BAX-inhibiting peptide, a suppressor of BAX translocation, decreased ROS generation and apoptosis in DLD-1.PUMA cells; (d) overexpression of PUMA induced up-regulation (>1.34-fold) of peroxiredoxin 1 and down-regulation (by 25%) of stathmin through proteasome-mediated degradation; and (e) hydrogen peroxide down-regulated stathmin and disrupted the cellular microtubule network. Our findings indicate that PUMA induces apoptosis, in part, through the BAX-dependent generation of superoxide and hydrogen peroxide. ROS overproduction and oxidative stress induce proteome-wise alterations, such as stathmin degradation and disorganization of the cell microtubule network, in apoptotic cells.</jats:p>
収録刊行物
-
- Cancer Research
-
Cancer Research 65 (5), 1647-1654, 2005-03-01
American Association for Cancer Research (AACR)
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1362825894887155456
-
- NII論文ID
- 30018588687
-
- ISSN
- 15387445
- 00085472
-
- データソース種別
-
- Crossref
- CiNii Articles