Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase

被引:47
作者
Pozuelo-Rubio, M. [1 ]
机构
[1] CSIC, Ctr Andaluz Biol Mol & Med Regenerat, Seville 41092, Spain
关键词
14-3-3; autophagy; starvation; C2-ceramide; hVps34; CELL-DEATH; FUNCTIONAL SPECIFICITY; 3-KINASE COMPLEX; INHIBITION; MACROAUTOPHAGY; KINASE; PHOSPHORYLATION; SURVIVAL; BINDING; DEGRADATION;
D O I
10.1038/cdd.2010.118
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
14-3-3s are binding proteins with survival functions in cells by interaction with proteins involved in the regulation of cell fate. The role of 14-3-3 during autophagy was investigated, thus, a forced expression of 14-3-3 zeta reduces C2-ceramide-induced autophagy, whereas depletion of 14-3-3 zeta promotes autophagy. The 14-3-3 role in autophagyc-related proteins was also investigated. The human vacuolar protein sorting 34 (hVps34), the class III phosphatidylinositol-3-kinase mediates multiple vesicle-trafficking processes such as endocytosis and autophagy, its activation being a requirement for autophagy initiation. Using chromatography techniques, hVps34 were eluted from a 14-3-3 affinity column, showing also a direct interaction with 14-3-3 proteins under physiological condition. Further analysis suggests that hVps34/14-3-3 association is a phorbol-12-myristate-13-acetate-dependent phosphorylated mechanism promoting a strong inhibition of the hVps34 lipid kinase activity, proteins kinase C being the likely kinase involved in phosphorylation and 14-3-3 binding of hVps34 under physiological conditions. Meanwhile, stimulation of autophagy leads to the dissociation of the 14-3-3/hVps34 complex enhancing hVps34 lipid kinase activity. Forced expression of 14-3-3 zeta reduces hVps34 kinase activity and depletion of 14-3-3 zeta promotes upregulation of this activity. In this study, 14-3-3 zeta proteins are shown as a negative regulator of autophagy through regulation of a key component of early stages of the autophagy pathway, such as hVps34. Cell Death and Differentiation (2011) 18, 479-492; doi:10.1038/cdd.2010.118; published online 1 October 2010
引用
收藏
页码:479 / 492
页数:14
相关论文
共 47 条
[1]   Functional specificity in 14-3-3 isoform interactions through dimer formation and phosphorylation. Chromosome location of mammalian isoforms and variants. [J].
Aitken, A .
PLANT MOLECULAR BIOLOGY, 2002, 50 (06) :993-1010
[2]   The regulation and function of Class III PI3Ks: novel roles for Vps34 [J].
Backer, Jonathan M. .
BIOCHEMICAL JOURNAL, 2008, 410 (01) :1-17
[3]   Inhibition of macroautophagy triggers apoptosis [J].
Boya, P ;
González-Polo, RA ;
Casares, N ;
Perfettini, JL ;
Dessen, P ;
Larochette, N ;
Métivier, D ;
Meley, D ;
Souquere, S ;
Yoshimori, T ;
Pierron, G ;
Codogno, P ;
Kroemer, G .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (03) :1025-1040
[4]  
CHEN CA, 1988, BIOTECHNIQUES, V6, P632
[5]   Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway [J].
Chen, Chia-Ling ;
Lin, Chiou-Feng ;
Chang, Wen-Tsan ;
Huang, Wei-Ching ;
Teng, Chiao-Fang ;
Lin, Yee-Shin .
BLOOD, 2008, 111 (08) :4365-4374
[6]   Lithium inhibits ceramide-and etoposide-induced protein phosphatase 2A methylation, Bcl-2 dephosphorylation, caspase-2 activation, and apoptosis [J].
Chen, Chia-Ling ;
Lin, Chiou-Feng ;
Chiang, Chi-Wu ;
Jan, Ming-Shiou ;
Lin, Yee-Shin .
MOLECULAR PHARMACOLOGY, 2006, 70 (02) :510-517
[7]   Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway [J].
Coward, Jesse ;
Ambrosini, Grazia ;
Musi, Elgilda ;
Truman, Jean-Philip ;
Haimovitz-Friedman, Adriana ;
Allegood, Jeremy C. ;
Wang, Elaine ;
Merrill, Alfred H., Jr. ;
Schwartz, Gary K. .
AUTOPHAGY, 2009, 5 (02) :184-193
[8]   Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells [J].
Daido, S ;
Kanzawa, T ;
Yamamoto, A ;
Takeuchi, H ;
Kondo, Y ;
Kondo, S .
CANCER RESEARCH, 2004, 64 (12) :4286-4293
[9]   Specificity and mechanism of action of some commonly used protein kinase inhibitors [J].
Davies, SP ;
Reddy, H ;
Caivano, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2000, 351 (351) :95-105
[10]   Negative Regulation of Vps34 by Cdk Mediated Phosphorylation [J].
Furuya, Tsuyoshi ;
Kim, Minsu ;
Lipinski, Marta ;
Li, Juying ;
Kim, Dohoon ;
Lu, Tao ;
Shen, Yong ;
Rameh, Lucia ;
Yankner, Bruce ;
Tsai, Li-Huei ;
Yuan, Junying .
MOLECULAR CELL, 2010, 38 (04) :500-511