Targeting PRAS40 for multiple diseases

被引：25

作者：

Chong, Zhao Zhong ^{[1
,2
]}

机构：

[1] Univ Illinois, Dept Anesthesiol, Chicago, IL 60607 USA

[2] Shandong Acad Med Sci, Inst Mat Med, Jinan, Peoples R China

来源：

DRUG DISCOVERY TODAY | 2016年 / 21卷 / 08期

关键词：

RICH AKT SUBSTRATE; 40 KDA PRAS40; OXIDATIVE STRESS; MAMMALIAN TARGET; UP-REGULATION; CELL-DEATH; PHOSPHATIDYLSERINE EXPOSURE; NEUROLOGICAL DISORDERS; MICROGLIAL ACTIVATION; INSULIN SENSITIVITY;

D O I：

10.1016/j.drudis.2016.04.005

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Proline-rich Akt substrate 40 kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40 results in its dissociation from mTORC1 and enhanced mTOR activation. PRAS40 in conjunction with mTORC1 has been closely associated with programmed cell death and is implicated in diabetes mellitus (DM), cardiovascular diseases, cancer, and neurological diseases. Thus, targeting PRAS40 might hold great promise for innovative therapeutic strategies for these diseases.

引用

页码：1222 / 1231

页数：10

共 109 条

[1]

Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid β-peptide (1-42), H2O2 and kainic acid:: implications for Alzheimer's disease [J].

Abdul, HM ;

Sultana, R ;

Keller, JN ;

St Clair, DK ;

Markesbery, WR ;

Butterfield, DA .

JOURNAL OF NEUROCHEMISTRY, 2006, 96 (05) :1322-1335

[2]

Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks [J].

Alers, Sebastian ;

Loeffler, Antje S. ;

Wesselborg, Sebastian ;

Stork, Bjoern .

MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (01) :2-11

[3]

Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease [J].

An, WL ;

Cowburn, RF ;

Li, L ;

Braak, H ;

Alafuzoff, I ;

Iqbal, K ;

Iqbal, IG ;

Winblad, B ;

Pei, JJ .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (02) :591-607

[4]

Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin [J].

Andreucci, M. ;

Fuiano, G. ;

Presta, P. ;

Lucisano, G. ;

Leone, F. ;

Fuiano, L. ;

Bisesti, V. ;

Esposito, P. ;

Russo, D. ;

Memoli, B. ;

Faga, T. ;

Michael, A. .

CELL PROLIFERATION, 2009, 42 (04) :554-561

[5]

Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor [J].

Avruch, Joseph ;

Long, Xiaomeng ;

Lin, Yenshou ;

Ortiz-Vega, Sara ;

Rapley, Joseph ;

Papageorgiou, Angela ;

Oshiro, Noriko ;

Kikkawa, Ushio .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2009, 37 :223-226

[6]

Life span extension and neuronal cell protection by Drosophila nicotinamidase [J].

Balan, Vitaly ;

Miller, Gregory S. ;

Kaplun, Ludmila ;

Balan, Karina ;

Chong, Zhao-Zhong ;

Li, Faqi ;

Kaplun, Alexander ;

VanBerkum, Mark F. A. ;

Arking, Robert ;

Freeman, D. Carl ;

Maiese, Kenneth ;

Tzivion, Guri .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (41) :27810-27819

[7]

Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1 [J].

Beugnet, A ;

Wang, XM ;

Proud, CG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (42) :40717-40722

[8]

PHOSPHORYLATION OF RIBOSOMAL-PROTEIN S6 IS INHIBITORY FOR AUTOPHAGY IN ISOLATED RAT HEPATOCYTES [J].

BLOMMAART, EFC ;

LUIKEN, JJFP ;

BLOMMAART, PJE ;

VANWOERKOM, GM ;

MEIJER, AJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (05) :2320-2326

[9]

Naturally Secreted Amyloid-β Increases Mammalian Target of Rapamycin (mTOR) Activity via a PRAS40-mediated Mechanism [J].

Caccamo, Antonella ;

Maldonado, Monica A. ;

Majumder, Smita ;

Medina, David X. ;

Holbein, Walter ;

Magri, Andrea ;

Oddo, Salvatore .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (11) :8924-8932

[10]

mTORC1 Phosphorylates the ULK1-mAtg13-FIP200 Autophagy Regulatory Complex [J].

Chan, Edmond Y. .

SCIENCE SIGNALING, 2009, 2 (84)

← 1 2 3 4 5 6 7 8 9 10 →