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Literature DB >> 25925668

Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy.

Jie Xu¹, Maryam Fotouhi², Peter S McPherson¹.

Abstract

Unc-51-like kinases (ULKs) are the most upstream kinases in the initiation of autophagy, yet the molecular mechanisms underlying their function are poorly understood. We report a new role for ULK in the induction of autophagy. ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12. Through binding to LC3 and associating with LC3-positive autophagosomes, active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.

Entities: Chemical Gene

Keywords: 14‐3‐3; DENN domain; GEF; LC3; guanine nucleotide exchange factor

Mesh：

Substances：

Year: 2015 PMID： 25925668 PMCID： PMC4467855 DOI： 10.15252/embr.201440006

Source DB: PubMed Journal: EMBO Rep ISSN： 1469-221X Impact factor: 8.807

31 in total

Review 1. Autophagy: renovation of cells and tissues.

Authors: Noboru Mizushima; Masaaki Komatsu
Journal: Cell Date: 2011-11-11 Impact factor: 41.582

Review 2. DENN domain proteins: regulators of Rab GTPases.

Authors: Andrea L Marat; Hatem Dokainish; Peter S McPherson
Journal: J Biol Chem Date: 2011-02-17 Impact factor: 5.157

3. Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells.

Authors: Moo-Seung Lee; Rama P Cherla; Matthew H Jenson; Dinorah Leyva-Illades; Margarita Martinez-Moczygemba; Vernon L Tesh
Journal: Cell Microbiol Date: 2011-07-04 Impact factor: 3.715

Review 4. How do 14-3-3 proteins work?-- Gatekeeper phosphorylation and the molecular anvil hypothesis.

Authors: Michael B Yaffe
Journal: FEBS Lett Date: 2002-02-20 Impact factor: 4.124

5. Small GTPase Rab12 regulates constitutive degradation of transferrin receptor.

Authors: Takahide Matsui; Takashi Itoh; Mitsunori Fukuda
Journal: Traffic Date: 2011-07-29 Impact factor: 6.215

6. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy.

Authors: Sabrina Di Bartolomeo; Marco Corazzari; Francesca Nazio; Serafina Oliverio; Gaia Lisi; Manuela Antonioli; Vittoria Pagliarini; Silvia Matteoni; Claudia Fuoco; Luigi Giunta; Marcello D'Amelio; Roberta Nardacci; Alessandra Romagnoli; Mauro Piacentini; Francesco Cecconi; Gian Maria Fimia
Journal: J Cell Biol Date: 2010-10-04 Impact factor: 10.539

7. Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.

Authors: Takahide Matsui; Mitsunori Fukuda
Journal: EMBO Rep Date: 2013-03-12 Impact factor: 8.807

8. Large scale screening for novel rab effectors reveals unexpected broad Rab binding specificity.

Authors: Mitsunori Fukuda; Eiko Kanno; Koutaro Ishibashi; Takashi Itoh
Journal: Mol Cell Proteomics Date: 2008-02-06 Impact factor: 5.911

9. Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase.

Authors: Daniel Papinski; Martina Schuschnig; Wolfgang Reiter; Larissa Wilhelm; Christopher A Barnes; Alessio Maiolica; Isabella Hansmann; Thaddaeus Pfaffenwimmer; Monika Kijanska; Ingrid Stoffel; Sung Sik Lee; Andrea Brezovich; Jane Hua Lou; Benjamin E Turk; Ruedi Aebersold; Gustav Ammerer; Matthias Peter; Claudine Kraft
Journal: Mol Cell Date: 2014-01-16 Impact factor: 17.970

10. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase.

Authors: Ryan C Russell; Ye Tian; Haixin Yuan; Hyun Woo Park; Yu-Yun Chang; Joungmok Kim; Haerin Kim; Thomas P Neufeld; Andrew Dillin; Kun-Liang Guan
Journal: Nat Cell Biol Date: 2013-05-19 Impact factor: 28.824

32 in total

Review 1. Deregulation of autophagy and vesicle trafficking in Parkinson's disease.

Authors: Patricia Sheehan; Zhenyu Yue
Journal: Neurosci Lett Date: 2018-04-05 Impact factor: 3.046

2. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.

Authors: Chantal Sellier; Maria-Letizia Campanari; Camille Julie Corbier; Angeline Gaucherot; Isabelle Kolb-Cheynel; Mustapha Oulad-Abdelghani; Frank Ruffenach; Adeline Page; Sorana Ciura; Edor Kabashi; Nicolas Charlet-Berguerand
Journal: EMBO J Date: 2016-04-21 Impact factor: 11.598

Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy.

Review 1. Autophagy: renovation of cells and tissues.

Review 2. DENN domain proteins: regulators of Rab GTPases.

3. Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells.

Review 4. How do 14-3-3 proteins work?-- Gatekeeper phosphorylation and the molecular anvil hypothesis.

5. Small GTPase Rab12 regulates constitutive degradation of transferrin receptor.

6. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy.

7. Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.

8. Large scale screening for novel rab effectors reveals unexpected broad Rab binding specificity.

9. Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase.

10. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase.

Review 1. Deregulation of autophagy and vesicle trafficking in Parkinson's disease.

2. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.

3. DENND3: a signaling/trafficking interface in autophagy.

4. Into the linker's DENN: A tyrosine's control of autophagy.

5. A new actin-binding domain glues autophagy together.

Review 6. 14-3-3 proteins: an important regulator of autophagy in diseases.

Review 7. Consequences of Rab GTPase dysfunction in genetic or acquired human diseases.

8. Regulation of DENND3, the exchange factor for the small GTPase Rab12 through an intramolecular interaction.

9. Poliovirus induces autophagic signaling independent of the ULK1 complex.

10. Intersectin-s interaction with DENND2B facilitates recycling of epidermal growth factor receptor.