![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 10, Issue 5, 1367-1379, May 1999
and
*Department of Biochemistry, Juntendo University School of
Medicine, Tokyo 113-8421, Japan; In the yeast Saccharomyces cerevisiae, the
Apg12p-Apg5p conjugating system is essential for autophagy.
Apg7p is required for the conjugation reaction, because Apg12p is
unable to form a conjugate with Apg5p in the apg7/cvt2
mutant. Apg7p shows a significant similarity to a ubiquitin-activating
enzyme, Uba1p. In this article, we investigated the function of Apg7p
as an Apg12p-activating enzyme. Hemagglutinin-tagged Apg12p was
coimmunoprecipitated with c-myc-tagged Apg7p. A two-hybrid experiment
confirmed the interaction. The coimmunoprecipitation was sensitive to a
thiol-reducing reagent. Furthermore, a thioester conjugate of Apg7p was
detected in a lysate of cells overexpressing both Apg7p and Apg12p.
These results indicated that Apg12p interacts with Apg7p via a
thioester bond. Mutational analyses of Apg7p suggested that
Cys507 of Apg7p is an active site cysteine and that both
the ATP-binding domain and the cysteine residue are essential for the
conjugation of Apg7p with Apg12p to form the Apg12p-Apg5p conjugate.
Cells expressing mutant Apg7ps, Apg7pG333A, or
Apg7pC507A showed defects in autophagy and
cytoplasm-to-vacuole targeting of aminopeptidase I. These results indicated that Apg7p functions as a novel
protein-activating enzyme necessary for Apg12p-Apg5p conjugation.
Department of Cell
Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan;
and Department of Bioscience, Teikyo University of
Science and Technology, Yamanashi 409-0193, Japan
This article has been cited by other articles:
|
|
 |
|
  M. Koike, M. Shibata, M. Tadakoshi, K. Gotoh, M. Komatsu, S. Waguri, N. Kawahara, K. Kuida, S. Nagata, E. Kominami, et al. Inhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Death after Hypoxic-Ischemic Injury Am. J. Pathol., February 1, 2008; 172(2): 454 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hanada, N. N. Noda, Y. Satomi, Y. Ichimura, Y. Fujioka, T. Takao, F. Inagaki, and Y. Ohsumi The Atg12-Atg5 Conjugate Has a Novel E3-like Activity for Protein Lipidation in Autophagy J. Biol. Chem., December 28, 2007; 282(52): 37298 - 37302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamada, N. N. Suzuki, T. Hanada, Y. Ichimura, H. Kumeta, Y. Fujioka, Y. Ohsumi, and F. Inagaki The Crystal Structure of Atg3, an Autophagy-related Ubiquitin Carrier Protein (E2) Enzyme that Mediates Atg8 Lipidation J. Biol. Chem., March 16, 2007; 282(11): 8036 - 8043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, E. Capan, Y. Zhao, J. Zhao, D. Stolz, S. C. Watkins, S. Jin, and B. Lu Autophagy Is Induced in CD4+ T Cells and Important for the Growth Factor-Withdrawal Cell Death J. Immunol., October 15, 2006; 177(8): 5163 - 5168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Tokgoz, R. N. Bohnsack, and A. L. Haas Pleiotropic Effects of ATP{middle dot}Mg2+ Binding in the Catalytic Cycle of Ubiquitin-activating Enzyme J. Biol. Chem., May 26, 2006; 281(21): 14729 - 14737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lavieu, F. Scarlatti, G. Sala, S. Carpentier, T. Levade, R. Ghidoni, J. Botti, and P. Codogno Regulation of Autophagy by Sphingosine Kinase 1 and Its Role in Cell Survival during Nutrient Starvation J. Biol. Chem., March 31, 2006; 281(13): 8518 - 8527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Iwata, J. Ezaki, M. Komatsu, S. Yokota, T. Ueno, I. Tanida, T. Chiba, K. Tanaka, and E. Kominami Excess Peroxisomes Are Degraded by Autophagic Machinery in Mammals J. Biol. Chem., February 17, 2006; 281(7): 4035 - 4041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kouno, M. Mizuguchi, I. Tanida, T. Ueno, T. Kanematsu, Y. Mori, H. Shinoda, M. Hirata, E. Kominami, and K. Kawano Solution Structure of Microtubule-associated Protein Light Chain 3 and Identification of Its Functional Subdomains J. Biol. Chem., July 1, 2005; 280(26): 24610 - 24617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Komatsu, S. Waguri, T. Ueno, J. Iwata, S. Murata, I. Tanida, J. Ezaki, N. Mizushima, Y. Ohsumi, Y. Uchiyama, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice J. Cell Biol., May 9, 2005; 169(3): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Klionsky The molecular machinery of autophagy: unanswered questions J. Cell Sci., January 1, 2005; 118(1): 7 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tanida, T. Ueno, and E. Kominami Human Light Chain 3/MAP1LC3B Is Cleaved at Its Carboxyl-terminal Met121 to Expose Gly120 for Lipidation and Targeting to Autophagosomal Membranes J. Biol. Chem., November 12, 2004; 279(46): 47704 - 47710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ichimura, Y. Imamura, K. Emoto, M. Umeda, T. Noda, and Y. Ohsumi In Vivo and in Vitro Reconstitution of Atg8 Conjugation Essential for Autophagy J. Biol. Chem., September 24, 2004; 279(39): 40584 - 40592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tanida, Y.-s. Sou, J. Ezaki, N. Minematsu-Ikeguchi, T. Ueno, and E. Kominami HsAtg4B/HsApg4B/Autophagin-1 Cleaves the Carboxyl Termini of Three Human Atg8 Homologues and Delipidates Microtubule-associated Protein Light Chain 3- and GABAA Receptor-associated Protein-Phospholipid Conjugates J. Biol. Chem., August 27, 2004; 279(35): 36268 - 36276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yu, A. Alva, H. Su, P. Dutt, E. Freundt, S. Welsh, E. H. Baehrecke, and M. J. Lenardo Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 Science, June 4, 2004; 304(5676): 1500 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Otto, M. Y. Wu, N. Kazgan, O. R. Anderson, and R. H. Kessin Dictyostelium Macroautophagy Mutants Vary in the Severity of Their Developmental Defects J. Biol. Chem., April 9, 2004; 279(15): 15621 - 15629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hemelaar, V. S. Lelyveld, B. M. Kessler, and H. L. Ploegh A Single Protease, Apg4B, Is Specific for the Autophagy-related Ubiquitin-like Proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L J. Biol. Chem., December 19, 2003; 278(51): 51841 - 51850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. He, Y. Dang, F. Dai, Z. Guo, J. Wu, X. She, Y. Pei, Y. Chen, W. Ling, C. Wu, et al. Post-translational Modifications of Three Members of the Human MAP1LC3 Family and Detection of a Novel Type of Modification for MAP1LC3B J. Biol. Chem., August 1, 2003; 278(31): 29278 - 29287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Bohnsack and A. L. Haas Conservation in the Mechanism of Nedd8 Activation by the Human AppBp1-Uba3 Heterodimer J. Biol. Chem., July 11, 2003; 278(29): 26823 - 26830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Brown, J. Liu, G.-C. Hung, D. Carter, D. Cui, and H.-L. Chiang The Vid Vesicle to Vacuole Trafficking Event Requires Components of the SNARE Membrane Fusion Machinery J. Biol. Chem., July 3, 2003; 278(28): 25688 - 25699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Otto, M. Y. Wu, N. Kazgan, O. R. Anderson, and R. H. Kessin Macroautophagy Is Required for Multicellular Development of the Social Amoeba Dictyostelium discoideum J. Biol. Chem., May 9, 2003; 278(20): 17636 - 17645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mizushima, A. Kuma, Y. Kobayashi, A. Yamamoto, M. Matsubae, T. Takao, T. Natsume, Y. Ohsumi, and T. Yoshimori Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate J. Cell Sci., May 1, 2003; 116(9): 1679 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Marino, J. A. Uria, X. S. Puente, V. Quesada, J. Bordallo, and C. Lopez-Otin Human Autophagins, a Family of Cysteine Proteinases Potentially Implicated in Cell Degradation by Autophagy J. Biol. Chem., January 31, 2003; 278(6): 3671 - 3678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-W. Wang, P. E. Stromhaug, J. Shima, and D. J. Klionsky The Ccz1-Mon1 Protein Complex Is Required for the Late Step of Multiple Vacuole Delivery Pathways J. Biol. Chem., November 27, 2002; 277(49): 47917 - 47927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hanaoka, T. Noda, Y. Shirano, T. Kato, H. Hayashi, D. Shibata, S. Tabata, and Y. Ohsumi Leaf Senescence and Starvation-Induced Chlorosis Are Accelerated by the Disruption of an Arabidopsis Autophagy Gene Plant Physiology, July 1, 2002; 129(3): 1181 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kuma, N. Mizushima, N. Ishihara, and Y. Ohsumi Formation of the ~350-kDa Apg12-Apg5{middle dot}Apg16 Multimeric Complex, Mediated by Apg16 Oligomerization, Is Essential for Autophagy in Yeast J. Biol. Chem., May 17, 2002; 277(21): 18619 - 18625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tanida, E. Tanida-Miyake, M. Komatsu, T. Ueno, and E. Kominami Human Apg3p/Aut1p Homologue Is an Authentic E2 Enzyme for Multiple Substrates, GATE-16, GABARAP, and MAP-LC3, and Facilitates the Conjugation of hApg12p to hApg5p J. Biol. Chem., April 12, 2002; 277(16): 13739 - 13744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Reggiori and D. J. Klionsky Autophagy in the Eukaryotic Cell Eukaryot. Cell, February 1, 2002; 1(1): 11 - 21. [Full Text] [PDF]
|
|
|
|
|
|
P. E. Stromhaug, A. Bevan, and W. A. Dunn Jr. GSA11 Encodes a Unique 208-kDa Protein Required for Pexophagy and Autophagy in Pichia pastoris J. Biol. Chem., November 2, 2001; 276(45): 42422 - 42435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishihara, M. Hamasaki, S. Yokota, K. Suzuki, Y. Kamada, A. Kihara, T. Yoshimori, T. Noda, and Y. Ohsumi Autophagosome Requires Specific Early Sec Proteins for Its Formation and NSF/SNARE for Vacuolar Fusion Mol. Biol. Cell, November 1, 2001; 12(11): 3690 - 3702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Dorn, W. A. Dunn Jr., and A. Progulske-Fox Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells Infect. Immun., September 1, 2001; 69(9): 5698 - 5708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Abeliovich and D. J. Klionsky Autophagy in Yeast: Mechanistic Insights and Physiological Function Microbiol. Mol. Biol. Rev., September 1, 2001; 65(3): 463 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, W. A. Wilson, M. A. Fujino, and P. J. Roach Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent Kinase Pho85p Mol. Cell. Biol., September 1, 2001; 21(17): 5742 - 5752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Drees, B. Sundin, E. Brazeau, J. P. Caviston, G.-C. Chen, W. Guo, K. G. Kozminski, M. W. Lau, J. J. Moskow, A. Tong, et al. A protein interaction map for cell polarity development J. Cell Biol., August 6, 2001; 154(3): 549 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, Y. Kamada, P. E. Stromhaug, J. Guan, A. Hefner-Gravink, M. Baba, S. V. Scott, Y. Ohsumi, W. A. Dunn , Jr., and D. J. Klionsky Cvt9/Gsa9 Functions in Sequestering Selective Cytosolic Cargo Destined for the Vacuole J. Cell Biol., April 16, 2001; 153(2): 381 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mizushima, A. Yamamoto, M. Hatano, Y. Kobayashi, Y. Kabeya, K. Suzuki, T. Tokuhisa, Y. Ohsumi, and T. Yoshimori Dissection of Autophagosome Formation using Apg5-deficient Mouse Embryonic Stem Cells J. Cell Biol., February 12, 2001; 152(4): 657 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, W.-P. Huang, and D. J. Klionsky Membrane Recruitment of Aut7p in the Autophagy and Cytoplasm to Vacuole Targeting Pathways Requires Aut1p, Aut2p, and the Autophagy Conjugation Complex J. Cell Biol., January 8, 2001; 152(1): 51 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Klionsky and S. D. Emr Autophagy as a Regulated Pathway of Cellular Degradation Science, December 1, 2000; 290(5497): 1717 - 1721. [Abstract] [Full Text]
|
|
|
|
|
|
O. Muller, T. Sattler, M. Flotenmeyer, H. Schwarz, H. Plattner, and A. Mayer Autophagic Tubes: Vacuolar Invaginations Involved in Lateral Membrane Sorting and Inverse Vesicle Budding J. Cell Biol., October 23, 2000; 151(3): 519 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kirisako, Y. Ichimura, H. Okada, Y. Kabeya, N. Mizushima, T. Yoshimori, M. Ohsumi, T. Takao, T. Noda, and Y. Ohsumi The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway J. Cell Biol., October 18, 2000; 151(2): 263 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Furukawa, N. Mizushima, T. Noda, and Y. Ohsumi A Protein Conjugation System in Yeast with Homology to Biosynthetic Enzyme Reaction of Prokaryotes J. Biol. Chem., March 10, 2000; 275(11): 7462 - 7465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. George, M. Baba, S. V. Scott, N. Mizushima, B. S. Garrison, Y. Ohsumi, and D. J. Klionsky Apg5p Functions in the Sequestration Step in the Cytoplasm-to-Vacuole Targeting and Macroautophagy Pathways Mol. Biol. Cell, March 1, 2000; 11(3): 969 - 982. [Abstract] [Full Text]
|
|
|
|
|
|
W.-P. Huang, S. V. Scott, J. Kim, and D. J. Klionsky The Itinerary of a Vesicle Component, Aut7p/Cvt5p, Terminates in the Yeast Vacuole via the Autophagy/Cvt Pathways J. Biol. Chem., February 25, 2000; 275(8): 5845 - 5851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Noda, J. Kim, W.-P. Huang, M. Baba, C. Tokunaga, Y. Ohsumi, and D. J. Klionsky Apg9p/Cvt7p Is an Integral Membrane Protein Required for Transport Vesicle Formation in the Cvt and Autophagy Pathways J. Cell Biol., February 7, 2000; 148(3): 465 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kirisako, M. Baba, N. Ishihara, K. Miyazawa, M. Ohsumi, T. Yoshimori, T. Noda, and Y. Ohsumi Formation Process of Autophagosome Is Traced with Apg8/Aut7p in Yeast J. Cell Biol., October 18, 1999; 147(2): 435 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, V. M. Dalton, K. P. Eggerton, S. V. Scott, and D. J. Klionsky Apg7p/Cvt2p Is Required for the Cytoplasm-to-Vacuole Targeting, Macroautophagy, and Peroxisome Degradation Pathways Mol. Biol. Cell, May 1, 1999; 10(5): 1337 - 1351. [Abstract] [Full Text]
|
|
|
|
|
|
W. Yuan, P. E. Strømhaug, and W. A. Dunn Jr. Glucose-induced Autophagy of Peroxisomes in Pichia pastoris Requires a Unique E1-like Protein Mol. Biol. Cell, May 1, 1999; 10(5): 1353 - 1366. [Abstract] [Full Text]
|
|
|
|
|
|
M. Hutchins, M Veenhuis, and D. Klionsky Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway J. Cell Sci., January 11, 1999; 112(22): 4079 - 4087. [Abstract] [PDF]
|
|
|
|
|
|
I. Tanida, E. Tanida-Miyake, T. Ueno, and E. Kominami The Human Homolog of Saccharomyces cerevisiae Apg7p Is a Protein-activating Enzyme for Multiple Substrates Including Human Apg12p, GATE-16, GABARAP, and MAP-LC3 J. Biol. Chem., January 12, 2001; 276(3): 1701 - 1706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mordier, C. Deval, D. Bechet, A. Tassa, and M. Ferrara Leucine Limitation Induces Autophagy and Activation of Lysosome-dependent Proteolysis in C2C12 Myotubes through a Mammalian Target of Rapamycin-independent Signaling Pathway J. Biol. Chem., September 15, 2000; 275(38): 29900 - 29906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Komatsu, I. Tanida, T. Ueno, M. Ohsumi, Y. Ohsumi, and E. Kominami The C-terminal Region of an Apg7p/Cvt2p Is Required for Homodimerization and Is Essential for Its E1 Activity and E1-E2 Complex Formation J. Biol. Chem., March 23, 2001; 276(13): 9846 - 9854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. U. Hutchins and D. J. Klionsky Vacuolar Localization of Oligomeric alpha -Mannosidase Requires the Cytoplasm to Vacuole Targeting and Autophagy Pathway Components in Saccharomyces cerevisiae J. Biol. Chem., June 1, 2001; 276(23): 20491 - 20498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shintani, K. Suzuki, Y. Kamada, T. Noda, and Y. Ohsumi Apg2p Functions in Autophagosome Formation on the Perivacuolar Structure J. Biol. Chem., August 3, 2001; 276(32): 30452 - 30460. [Abstract] [Full Text] [PDF]
|
|
