ANAT: A tool for constructing and analyzing functional protein networks

Science Signaling

Volumn 4, Issue 196, 2011, Pages

  Yosef, Nir ^a,b   Zalckvar, Einat ^c   Rubinstein, Assaf D ^c   Homilius, Max ^d   Atias, Nir ^e   Vardi, Liram ^e   Berman, Igor ^e   Zur, Hadas ^e   Kimchi, Adi ^c   Ruppin, Eytan ^e   Sharan, Roded ^e  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^d FREIE UNIVERSITÄT BERLIN   (Germany)

^e TEL AVIV UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; PROTEIN;

ADVANCED NETWORK ANALYSIS TOOL; APOPTOSIS; AUTOPHAGY; COMPUTER NETWORK; COMPUTER PROGRAM; DATA ANALYSIS SOFTWARE; PRIORITY JOURNAL; PROTEIN FUNCTION; QUALITY CONTROL; REVIEW; ALGORITHM; ANIMAL; ARABIDOPSIS; ARTICLE; BIOLOGICAL MODEL; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; ESCHERICHIA COLI; GENETICS; GENOME; HELICOBACTER PYLORI; HUMAN; INTERNET; METABOLISM; METHODOLOGY; MOUSE; PHYSIOLOGY; PLASMODIUM FALCIPARUM; PROTEIN ANALYSIS; RAT; REPRODUCIBILITY; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION;

ALGORITHMS; ANIMALS; APOPTOSIS; ARABIDOPSIS; AUTOPHAGY; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; ESCHERICHIA COLI; GENOME; HELICOBACTER PYLORI; HUMANS; INTERNET; MICE; MODELS, BIOLOGICAL; PLASMODIUM FALCIPARUM; PROTEIN INTERACTION MAPPING; PROTEINS; RATS; REPRODUCIBILITY OF RESULTS; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; SOFTWARE;

EID: 80054924924     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001935     Document Type: Review

References (64)

1. S. J. Wodak, S. Pu, J. Vlasblom, B. Séraphin, Challenges and rewards of interaction proteomics. Mol. Cell. Proteomics 8, 3-18 (2009).
2. E. Yeger-Lotem, L. Riva, L. J. Su, A. D. Gitler, A. G. Cashikar, O. D. King, P. K. Auluck, M. L. Geddie, J. S. Valastyan, D. R. Karger, S. Lindquist, E. Fraenkel, Bridging highthroughput genetic and transcriptional data reveals cellular responses to α-synuclein toxicity. Nat. Genet. 41, 316-323 (2009).
3. M. A. Pujana, J. D. Han, L. M. Starita, K. N. Stevens, M. Tewari, J. S. Ahn, G. Rennert, V. Moreno, T. Kirchhoff, B. Gold, V. Assmann, W. M. Elshamy, J. F. Rual, D. Levine, L. S. Rozek, R. S. Gelman, K. C. Gunsalus, R. A. Greenberg, B. Sobhian, N. Bertin, K. Venkatesan, N. Ayivi-Guedehoussou, X. Solé, P. Hernández, C. Lázaro, K. L. Nathanson, B. L. Weber, M. E. Cusick, D. E. Hill, K. Offit, D. M. Livingston, S. B. Gruber, J. D. Parvin, M. Vidal, Network modeling links breast cancer susceptibility and centrosome dys function. Nat. Genet. 39, 1338-1349 (2007).
4. H. Goehler, M. Lalowski, U. Stelzl, S. Waelter, M. Stroedicke, U. Worm, A. Droege, K. S. Lindenberg, M. Knoblich, C. Haenig, M. Herbst, J. Suopanki, E. Scherzinger, C. Abraham, B. Bauer, R. Hasenbank, A. Fritzsche, A. H. Ludewig, K. Büssow, S. H. Coleman, C. A. Gutekunst, B. G. Landwehrmeyer, H. Lehrach, E. E. Wanker, A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol. Cell 15, 853-865 (2004).
5. S. E. Calvano, W. Xiao, D. R. Richards, R. M. Felciano, H. V. Baker, R. J. Cho, R. O. Chen, B. H. Brownstein, J. P. Cobb, S. K. Tschoeke, C. Miller-Graziano, L. L. Moldawer, M. N. Mindrinos, R. W. Davis, R. G. Tompkins, S. F. Lowry; Inflamm and Host Response to Injury Large Scale Collab. Res. Program, A network-based analysis of systemic inflammation in humans. Nature 437, 1032-1037 (2005).
6. M. R. Said, T. J. Begley, A. V. Oppenheim, D. A. Lauffenburger, L. D. Samson, Global network analysis of phenotypic effects: Protein networks and toxicity modulation in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 101, 18006-18011 (2004).
7. M. S. Scott, T. Perkins, S. Bunnell, F. Pepin, D. Y. Thomas, M. Hallett, Identifying regulatory subnetworks for a set of genes. Mol. Cell. Proteomics 4, 683-692 (2005).
8. N. Yosef, L. Ungar, E. Zalckvar, A. Kimchi, M. Kupiec, E. Ruppin, R. Sharan, Toward accurate reconstruction of functional protein networks. Mol. Syst. Biol. 5, 248 (2009).
9. S. Rashi-Elkeles, R. Elkon, N. Weizman, C. Linhart, N. Amariglio, G. Sternberg, G. Rechavi, A. Barzilai, R. Shamir, Y. Shiloh, Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue. Oncogene 25, 1584-1592 (2006).
10. F. Iragne, M. Nikolski, B. Mathieu, D. Auber, D. Sherman, ProViz: Protein interaction visualization and exploration. Bioinformatics 21, 272-274 (2005).
11. C. L. Myers, D. Robson, A. Wible, M. A. Hibbs, C. Chiriac, C. L. Theesfeld, K. Dolinski, O. G. Troyanskaya, Discovery of biological networks from diverse functional genomic data. Genome Biol. 6, R114 (2005).
12. E. G. Cerami, G. D. Bader, B. E. Gross, C. Sander, cPath: Open source software for collecting, storing, and querying biological pathways. BMC Bioinformatics 7, 497 (2006).
13. R. Aragues, D. Jaeggi, B. Oliva, PIANA: Protein interactions and network analysis. Bioinformatics 22, 1015-1017 (2006).
14. S. I. Berger, J. M. Posner, A. Ma'ayan, Genes2Networks: Connecting lists of gene symbols using mammalian protein interactions databases. BMC Bioinformatics 8, 372 (2007).
15. M. S. Cline, M. Smoot, E. Cerami, A. Kuchinsky, N. Landys, C. Workman, R. Christmas, I. Avila-Campilo, M. Creech, B. Gross, K. Hanspers, R. Isserlin, R. Kelley, S. Killcoyne, S. Lotia, S. Maere, J. Morris, K. Ono, V. Pavlovic, A. R. Pico, A. Vailaya, P. L. Wang, A. Adler, B. R. Conklin, L. Hood, M. Kuiper, C. Sander, I. Schmulevich, B. Schwikowski, G. J. Warner, T. Ideker, G. D. Bader, Integration of biological networks and gene expression data using Cytoscape. Nat. Protoc. 2, 2366-2382 (2007).
16. A. Alexeyenko, E. L. Sonnhammer, Global networks of functional coupling in eukaryotes from comprehensive data integration. Genome Res. 19, 1107-1116 (2009).
17. A. V. Antonov, S. Dietmann, I. Rodchenkov, H. W. Mewes, PPI spider: A tool for the interpretation of proteomics data in the context of protein-protein interaction networks. Proteomics 9, 2740-2749 (2009).
18. J. H. Konieczka, K. Drew, A. Pine, K. Belasco, S. Davey, T. A. Yatskievych, R. Bonneau, P. B. Antin, BioNetBuilder2.0: Bringing systems biology to chicken and other model organisms. BMC Genomics 10 (suppl. 2), S6 (2009).
19. A. Martin, M. E. Ochagavia, L. C. Rabasa, J. Miranda, J. Fernandez-de-Cossio, R. Bringas, BisoGenet: A new tool for gene network building, visualization and analysis. BMC Bioinformatics 11, 91 (2010).
20. D. Szklarczyk, A. Franceschini, M. Kuhn, M. Simonovic, A. Roth, P. Minguez, T. Doerks, M. Stark, J. Muller, P. Bork, L. J. Jensen, C. von Mering, The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39 (Database issue), D561-D568 (2011).
21. M. Laakso, S. Hautaniemi, Integrative platform to translate gene sets to networks. Bioinformatics 26, 1802-1803 (2010).
22. R. Elkon, R. Vesterman, N. Amit, I. Ulitsky, I. Zohar, M. Weisz, G. Mass, N. Orlev, G. Sternberg, R. Blekhman, J. Assa, Y. Shiloh, R. Shamir, SPIKE - A database, visualization and analysis tool of cellular signaling pathways. BMC Bioinformatics 9, 110 (2008).
23. E. Demir, O. Babur, U. Dogrusoz, A. Gursoy, G. Nisanci, R. Cetin-Atalay, M. Ozturk, PATIKA: An integrated visual environment for collaborative construction and analysis of cellular pathways. Bioinformatics 18, 996-1003 (2002).
24. J. Chen, E. E. Bardes, B. J. Aronow, A. G. Jegga, ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37 (Web Server issue), W305-W311 (2009).
25. J. Montojo, K. Zuberi, H. Rodriguez, F. Kazi, G. Wright, S. L. Donaldson, Q. Morris, G. D. Bader, GeneMANIA Cytoscape plugin: Fast gene function predictions on the desktop. Bioinformatics 26, 2927-2928 (2010).
26. A. Subramanian, P. Tamayo, V. K. Mootha, S. Mukherjee, B. L. Ebert, M. A. Gillette, A. Paulovich, S. L. Pomeroy, T. R. Golub, E. S. Lander, J. P. Mesirov, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U.S.A. 102, 15545-15550 (2005).
27. T. Ideker, O. Ozier, B. Schwikowski, A. F. Siegel, Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 18 (suppl. 1), S233-S240 (2002).
28. I. Ulitsky, R. Shamir, Identification of functional modules using network topology and high-throughput data. BMC Syst. Biol. 1, 8 (2007).
29. D. Beisser, G. W. Klau, T. Dandekar, T. Müller, M. T. Dittrich, BioNet: An R-Package for the functional analysis of biological networks. Bioinformatics 26, 1129-1130 (2010).
30. A. Nikitin, S. Egorov, N. Daraselia, I. Mazo, Pathway studio - the analysis and navigation of molecular networks. Bioinformatics 19, 2155-2157 (2003).
31. J. C. Rain, L. Selig, H. De Reuse, V. Battaglia, C. Reverdy, S. Simon, G. Lenzen, F. Petel, J. Wojcik, V. Schächter, Y. Chemama, A. Labigne, P. Legrain, The protein-protein interaction map of Helicobacter pylori. Nature 409, 211-215 (2001).
32. S. Li, C. M. Armstrong, N. Bertin, H. Ge, S. Milstein, M. Boxem, P. O. Vidalain, J. D. Han, A. Chesneau, T. Hao, D. S. Goldberg, N. Li, M. Martinez, J. F. Rual, P. Lamesch, L. Xu, M. Tewari, S. L. Wong, L. V. Zhang, G. F. Berriz, L. Jacotot, P. Vaglio, J. Reboul, T. Hirozane-Kishikawa, Q. Li, H. W. Gabel, A. Elewa, B. Baumgartner, D. J. Rose, H. Yu, S. Bosak, R. Sequerra, A. Fraser, S. E. Mango, W. M. Saxton, S. Strome, S. Van Den Heuvel, F. Piano, J. Vandenhaute, C. Sardet, M. Gerstein, L. Doucette-Stamm, K. C. Gunsalus, J. W. Harper, M. E. Cusick, F. P. Roth, D. E. Hill, M. Vidal, A map of the interactome network of the metazoan C. elegans. Science 303, 540-543 (2004).
33. D. J. LaCount, M. Vignali, R. Chettier, A. Phansalkar, R. Bell, J. R. Hesselberth, L. W. Schoenfeld, I. Ota, S. Sahasrabudhe, C. Kurschner, S. Fields, R. E. Hughes, A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438, 103-107 (2005).
34. L. Giot, J. S. Bader, C. Brouwer, A. Chaudhuri, B. Kuang, Y. Li, Y. L. Hao, C. E. Ooi, B. Godwin, E. Vitols, G. Vijayadamodar, P. Pochart, H. Machineni, M. Welsh, Y. Kong, B. Zerhusen, R. Malcolm, Z. Varrone, A. Collis, M. Minto, S. Burgess, L. McDaniel, E. Stimpson, F. Spriggs, J. Williams, K. Neurath, N. Ioime, M. Agee, E. Voss, K. Furtak, R. Renzulli, N. Aanensen, S. Carrolla, E. Bickelhaupt, Y. Lazovatsky, A. DaSilva, J. Zhong, C. A. Stanyon, R. L. Finley, Jr, K. P. White, M. Braverman, T. Jarvie, S. Gold, M. Leach, J. Knight, R. A. Shimkets, M. P. McKenna, J. Chant, J. M. Rothberg, A protein interaction map of Drosophila melanogaster. Science 302, 1727-1736 (2003).
35. J. F. Rual, K. Venkatesan, T. Hao, T. Hirozane-Kishikawa, A. Dricot, N. Li, G. F. Berriz, F. D. Gibbons, M. Dreze, N. Ayivi-Guedehoussou, N. Klitgord, C. Simon, M. Boxem, S. Milstein, J. Rosenberg, D. S. Goldberg, L. V. Zhang, S. L. Wong, G. Franklin, S. Li, J. S. Albala, J. Lim, C. Fraughton, E. Llamosas, S. Cevik, C. Bex, P. Lamesch, R. S. Sikorski, J. Vandenhaute, H. Y. Zoghbi, A. Smolyar, S. Bosak, R. Sequerra, L. Doucette-Stamm, M. E. Cusick, D. E. Hill, F. P. Roth, M. Vidal, Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173-1178 (2005).
36. U. Stelzl, U. Worm, M. Lalowski, C. Haenig, F. H. Brembeck, H. Goehler, M. Stroedicke, M. Zenkner, A. Schoenherr, S. Koeppen, J. Timm, S. Mintzlaff, C. Abraham, N. Bock, S. Kietzmann, A. Goedde, E. Toksöz, A. Droege, S. Krobitsch, B. Korn, W. Birchmeier, H. Lehrach, E. E. Wanker, A human protein-protein interaction network: A resource for annotating the proteome. Cell 122, 957-968 (2005).
37. R. M. Ewing, P. Chu, F. Elisma, H. Li, P. Taylor, S. Climie, L. McBroom-Cerajewski, M. D. Robinson, L. O'Connor, M. Li, R. Taylor, M. Dharsee, Y. Ho, A. Heilbut, L. Moore, S. Zhang, O. Ornatsky, Y. V. Bukhman, M. Ethier, Y. Sheng, J. Vasilescu, M. Abu-Farha, J. P. Lambert, H. S. Duewel, I. I. Stewart, B. Kuehl, K. Hogue, K. Colwill, K. Gladwish, B. Muskat, R. Kinach, S. L. Adams, M. F. Moran, G. B. Morin, T. Topaloglou, D. Figeys, Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol. Syst. Biol. 3, 89 (2007).
38. M. Arifuzzaman, M. Maeda, A. Itoh, K. Nishikata, C. Takita, R. Saito, T. Ara, K. Nakahigashi, H. C. Huang, A. Hirai, K. Tsuzuki, S. Nakamura, M. Altaf-Ul-Amin, T. Oshima, T. Baba, N. Yamamoto, T. Kawamura, T. Ioka-Nakamichi, M. Kitagawa, M. Tomita, S. Kanaya, C. Wada, H. Mori, Large-scale identification of protein-protein interaction of Escherichia coli K-12. Genome Res. 16, 686-691 (2006).
39. H. Yu, N. M. Luscombe, H. X. Lu, X. Zhu, Y. Xia, J. D. Han, N. Bertin, S. Chung, M. Vidal, M. Gerstein, Annotation transfer between genomes: Protein-protein interologs and protein-DNA regulogs. Genome Res. 14, 1107-1118 (2004).
40. B. J. Breitkreutz, C. Stark, T. Reguly, L. Boucher, A. Breitkreutz, M. Livstone, R. Oughtred, D. H. Lackner, J. Bähler, V. Wood, K. Dolinski, M. Tyers, The BioGRID Interaction Database: 2008 update. Nucleic Acids Res. 36 (Database issue), D637-D640 (2008).
41. I. Xenarios, L. Salwínski, X. J. Duan, P. Higney, S. M. Kim, D. Eisenberg, DIP, the Database of Interacting Proteins: A research tool for studying cellular networks of protein interactions. Nucleic Acids Res. 30, 303-305 (2002).
42. S. Peri, J. D. Navarro, R. Amanchy, T. Z. Kristiansen, C. K. Jonnalagadda, V. Surendranath, V. Niranjan, B. Muthusamy, T. K. Gandhi, M. Gronborg, N. Ibarrola, N. Deshpande, K. Shanker, H. N. Shivashankar, B. P. Rashmi, M. A. Ramya, Z. Zhao, K. N. Chandrika, N. Padma, H. C. Harsha, A. J. Yatish, M. P. Kavitha, M. Menezes, D. R. Choudhury, S. Suresh, N. Ghosh, R. Saravana, S. Chandran, S. Krishna, M. Joy, S. K. Anand, V. Madavan, A. Joseph, G. W. Wong, W. P. Schiemann, S. N. Constantinescu, L. Huang, R. Khosravi-Far, H. Steen, M. Tewari, S. Ghaffari, G. C. Blobe, C. V. Dang, J. G. Garcia, J. Pevsner, O. N. Jensen, P. Roepstorff, K. S. Deshpande, A. M. Chinnaiyan, A. Hamosh, A. Chakravarti, A. Pandey, Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 13, 2363-2371 (2003).
43. A. Lachmann, H. Xu, J. Krishnan, S. I. Berger, A. R. Mazloom, A. Ma'ayan, ChEA: Transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26, 2438-2444 (2010).
44. T. I. Lee, N. J. Rinaldi, F. Robert, D. T. Odom, Z. Bar-Joseph, G. K. Gerber, N. M. Hannett, C. T. Harbison, C. M. Thompson, I. Simon, J. Zeitlinger, E. G. Jennings, H. L. Murray, D. B. Gordon, B. Ren, J. J. Wyrick, J. B. Tagne, T. L. Volkert, E. Fraenkel, D. K. Gifford, R. A. Young, Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799-804 (2002).
45. H. Y. Chuang, E. Lee, Y. T. Liu, D. Lee, T. Ideker, Network-based classification of breast cancer metastasis. Mol. Syst. Biol. 3, 140 (2007).
46. M. A. Harris, J. Clark, A. Ireland, J. Lomax, M. Ashburner, R. Foulger, K. Eilbeck, S. Lewis, B. Marshall, C. Mungall, J. Richter, G. M. Rubin, J. A. Blake, C. Bult, M. Dolan, H. Drabkin, J. T. Eppig, D. P. Hill, L. Ni, M. Ringwald, R. Balakrishnan, J. M. Cherry, K. R. Christie, M. C. Costanzo, S. S. Dwight, S. Engel, D. G. Fisk, J. E. Hirschman, E. L. Hong, R. S. Nash, A. Sethuraman, C. L. Theesfeld, D. Botstein, K. Dolinski, B. Feierbach, T. Berardini, S. Mundodi, S. Y. Rhee, R. Apweiler, D. Barrell, E. Camon, E. Dimmer, V. Lee, R. Chisholm, P. Gaudet, W. Kibbe, R. Kishore, E. M. Schwarz, P. Sternberg, M. Gwinn, L. Hannick, J. Wortman, M. Berriman, V. Wood, N. de la Cruz, P. Tonellato, P. Jaiswal, T. Seigfried, R. White, Gene Ontology Consortium, The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32 (database issue), D258-D261 (2004).
47. M. Kanehisa, The KEGG database. Novartis Found. Symp. 247, 91-101, discussion 101-103, 119-128, 244-252 (2002).
48. R. Mathew, C. M. Karp, B. Beaudoin, N. Vuong, G. Chen, H. Y. Chen, K. Bray, A. Reddy, G. Bhanot, C. Gelinas, R. S. Dipaola, V. Karantza-Wadsworth, E. White, Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062-1075 (2009).
49. J. Moscat, M. T. Diaz-Meco, p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137, 1001-1004 (2009).
50. E. Zalckvar, N. Yosef, S. Reef, Y. Ber, A. D. Rubinstein, I. Mor, R. Sharan, E. Ruppin, A. Kimchi, A systems level strategy for analyzing the cell death network: Implication in exploring the apoptosis/autophagy connection. Cell Death Differ. 17, 1244-1253 (2010).
51. T. de Lange, Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110 (2005).
52. K. Collins, J. R. Mitchell, Telomerase in the human organism. Oncogene 21, 564-579 (2002).
53. S. H. Askree, T. Yehuda, S. Smolikov, R. Gurevich, J. Hawk, C. Coker, A. Krauskopf, M. Kupiec, M. J. McEachern, A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc. Natl. Acad. Sci. U.S.A. 101, 8658-8663 (2004).
54. T. Gatbonton, M. Imbesi, M. Nelson, J. M. Akey, D. M. Ruderfer, L. Kruglyak, J. A. Simon, A. Bedalov, Telomere length as a quantitative trait: Genome-wide survey and genetic mapping of telomere length-control genes in yeast. PLoS Genet. 2, e35 (2006).
55. L. Ungar, N. Yosef, Y. Sela, R. Sharan, E. Ruppin, M. Kupiec, A genome-wide screen for essential yeast genes that affect telomere length maintenance. Nucleic Acids Res. 37, 3840-3849 (2009).
56. N. Yosef, M. Kupiec, E. Ruppin, R. Sharan, A complex-centric view of protein network evolution. Nucleic Acids Res. 37, e88 (2009).
57. R. Shachar, L. Ungar, M. Kupiec, E. Ruppin, R. Sharan, A systems-level approach to mapping the telomere length maintenance gene circuitry. Mol. Syst. Biol. 4, 172 (2008).
58. S. Khuller, B. Raghavachari, N. Young, Balancing minimum spanning trees and shortest-path trees. Algorithmica 14, 305-321 (1995).
59. D. A. Nelson, T. T. Tan, A. B. Rabson, D. Anderson, K. Degenhardt, E. White, Hypoxia and defective apoptosis drive genomic instability and tumorigenesis. Genes Dev. 18, 2095-2107 (2004).
60. L. Galluzzi, M. C. Maiuri, I. Vitale, H. Zischka, M. Castedo, L. Zitvogel, G. Kroemer, Cell death modalities: Classification and pathophysiological implications. Cell Death Differ. 14, 1237-1243 (2007).
61. A. Eisenberg-Lerner, S. Bialik, H. U. Simon, A. Kimchi, Life and death partners: Apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 16, 966-975 (2009).
62. D. L. Vaux, J. Silke, IAPs, RINGs and ubiquitylation. Nat. Rev. Mol. Cell Biol. 6, 287-297 (2005).
63. M. Komatsu, S. Waguri, M. Koike, Y. S. Sou, T. Ueno, T. Hara, N. Mizushima, J. Iwata, J. Ezaki, S. Murata, J. Hamazaki, Y. Nishito, S. Iemura, T. Natsume, T. Yanagawa, J. Uwayama, E. Warabi, H. Yoshida, T. Ishii, A. Kobayashi, M. Yamamoto, Z. Yue, Y. Uchiyama, E. Kominami, K. Tanaka, Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163 (2007).
64. Acknowledgments: The work is dedicated to the memory of Dr. Anat Krauskopf, who passed away after a brave battle against breast cancer (see http;//www.tau.ac.il/lifesci/ biotechnology/krauskopf/krauskopf.html). Funding: This research was supported by a Bikura grant from the Israel Science Foundation (A.K., E.R., and R.S.) and by a Center of Excellence grant from the Flight Attendant Medical Research Institute (A.K.).