ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells

被引：56

作者：

Ci, Y. ^{[1
,2
,3
]}

Shi, K. ^{[1
,2
,3
]}

An, J. ^{[1
,2
,3
]}

Yang, Y. ^{[1
,2
,3
]}

Hui, K. ^{[1
,2
,3
]}

Wu, P. ^{[1
,2
,3
]}

Shi, L. ^{[1
,2
,3
]}

Xu, C. ^{[1
,2
,3
]}

机构：

[1] Peking Union Med Coll, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China

[2] Peking Union Med Coll, Sch Basic Med, Dept Biochem & Mol Biol, Beijing 100005, Peoples R China

[3] Chinese Acad Med Sci, Beijing 100730, Peoples R China

来源：

CELL DEATH & DISEASE | 2014年 / 5卷

关键词：

APOPTOSIS IN-VITRO; SODIUM SELENITE; DEATH; ACTIVATION; PROTEIN; MTOR; INDUCTION; LEUKEMIA; COMPLEX; MACROAUTOPHAGY;

D O I：

10.1038/cddis.2014.506

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Reactive oxygen species (ROS) have an important role in regulating various cellular processes. Our previous study confirmed that selenite, an anti-tumour agent, triggered apoptosis through the production of ROS in multiple types of cancer cells. In this study, we discovered that ROS also inhibited protective autophagy by decreasing the expression of ULK1, an initiator of autophagy, in selenite-treated NB4 cells. Further experiments demonstrated that p-p53 (S392), a phosphorylation event promoted by p70S6K, bound to the promoter of ULK1 and modulated its expression. Experiments in a mouse tumour model with NB4 cells provided in vivo confirmation of the alterations in the p70S6K/p53/ULK1 axis. Collectively, our results show that ROS inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells.

引用

页码：e1542 / e1542

页数：10

共 46 条

[1] The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo [J].

An, J. J. ;

Shi, K. J. ;

Wei, W. ;

Hua, F. Y. ;

Ci, Y. L. ;

Jiang, Q. ;

Li, F. ;

Wu, P. ;

Hui, K. Y. ;

Yang, Y. ;

Xu, C. M. .

CELL DEATH & DISEASE, 2013, 4 :e973-e973

[2]

Azad MB, 2009, ANTIOXID REDOX SIGN, V11, P777, DOI 10.1089/ARS.2008.2270

[3] p53 and ARF: unexpected players in autophagy [J].

Balaburski, Gregor M. ;

Hontz, Robert D. ;

Murphy, Maureen E. .

TRENDS IN CELL BIOLOGY, 2010, 20 (06) :363-369

[4] RAPAMYCIN FKBP SPECIFICALLY BLOCKS GROWTH-DEPENDENT ACTIVATION OF AND SIGNALING BY THE 70 KD S6 PROTEIN-KINASES [J].

CHUNG, J ;

KUO, CJ ;

CRABTREE, GR ;

BLENIS, J .

CELL, 1992, 69 (07) :1227-1236

[5] mTOR/p70S6K signaling distinguishes routine, maintenance-level autophagy from autophagic cell death during influenza A infection [J].

Datan, Emmanuel ;

Shirazian, Alireza ;

Benjamin, Shawna ;

Matassov, Demetrius ;

Tinari, Antonella ;

Malorni, Walter ;

Lockshin, Richard A. ;

Garcia-Sastre, Adolfo ;

Zakeri, Zahra .

VIROLOGY, 2014, 452 :175-190

[6] Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis [J].

De Nicola, Gina M. ;

Karreth, Florian A. ;

Humpton, Timothy J. ;

Gopinathan, Aarthi ;

Wei, Cong ;

Frese, Kristopher ;

Mangal, Dipti ;

Yu, Kenneth H. ;

Yeo, Charles J. ;

Calhoun, Eric S. ;

Scrimieri, Francesca ;

Winter, Jordan M. ;

Hruban, Ralph H. ;

Iacobuzio-Donahue, Christine ;

Kern, Scott E. ;

Blair, Ian A. ;

Tuveson, David A. .

NATURE, 2011, 475 (7354) :106-U128

[7] NF-κB activation represses tumor necrosis factor-α-induced autophagy [J].

Djavaheri-Mergny, Mojgan ;

Amelotti, Manuela ;

Mathieu, Julie ;

Besancon, Francoise ;

Bauvy, Chantal ;

Souquere, Sylvie ;

Pierron, Gerard ;

Codogno, Patrice .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (41) :30373-30382

[8] Mapping the Phosphorylation Sites of Ulk1 [J].

Dorsey, Frank C. ;

Rose, Kristie L. ;

Coenen, Silvia ;

Prater, Stephanie M. ;

Cavett, Valerie ;

Cleveland, John L. ;

Caldwell-Busby, Jennifer .

JOURNAL OF PROTEOME RESEARCH, 2009, 8 (11) :5253-5263

[9] Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy [J].

Egan, Daniel F. ;

Shackelford, David B. ;

Mihaylova, Maria M. ;

Gelino, Sara ;

Kohnz, Rebecca A. ;

Mair, William ;

Vasquez, Debbie S. ;

Joshi, Aashish ;

Gwinn, Dana M. ;

Taylor, Rebecca ;

Asara, John M. ;

Fitzpatrick, James ;

Dillin, Andrew ;

Viollet, Benoit ;

Kundu, Mondira ;

Hansen, Malene ;

Shaw, Reuben J. .

SCIENCE, 2011, 331 (6016) :456-461

[10] Alpha-eleostearic acid induces autophagy-dependent cell death through targeting AKT/mTOR and ERK1/2 signal together with the generation of reactive oxygen species [J].

Eom, Jung-Min ;

Seo, Min-Ji ;

Baek, Ji-Young ;

Chu, Hyuk ;

Han, Seung Hyun ;

Min, Tae Sun ;

Cho, Chong-Su ;

Yun, Cheol-Heui .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 391 (01) :903-908

← 1 2 3 4 5 →