Protein complexes as functional machines in normal physiology and human disease There is growing appreciation that many cellular processes are carried out by proteins assembled into multi-component 'machines' which often act coordinately with other biochemical machines, akin to an assembly line. We have an intense interest in characterizing protein complexes and their dynamic response under normal physiologic conditions. These results provide a baseline for us to understand how individual complexes or biochemical networks are functionally disrupted by disease-specific proteoforms, gene variants, infectious pathogens, or other exogenous factors. Collectively, these data can address mechanistic gaps in our interpretation of genotype-phenotype relationships and represent an important step towards a comprehensive characterization of biochemical pathways which support cellular function. See papers below and our resources page for more information.
Publications related to biochemical networks and protein complexes 29. Miotto B, Marchal C, Adelmant G, Guinot N, Xie P, Marto JA, Zhang L, Defossez PA. Stabilization of the methyl-cpg binding protein zbtb38 by the deubiquitinase USP9X limits the occurrence of toxicity of oxidative stress in human cells. Nucl Acids Res 2018;46:4392-4404.
28. Cato L, Neeb A, Sharp A, Buzon V, Ficarro SB, Yang L, Muhle-Goll C, Kuznik NC, Riisnaes R, Rodrigues DN, Armant O, Gourain V, Adelmant G, Ntim EA, Westerling T, Dolling D, Rescigno P, Figueiredo I, Fauser F, Wu J, Shatkina L, Ester C, Luy B, Puchta H, Strahle U, Marto JA, Nienhaus U, Al-Lazikani B, Salvatella X, de Bono J, Cato ACB, Brown M. Targeting the androgen receptor n-terminus via the cochaperone bag-1l. eLife 2017; Aug 10;6. pii: e27159.
27. Ferry L, Fournier A, Tsusaka T, Adelmant G, Shimazu T, Matano S, Kirsh O, Amouroux R, Dohmae N, Suzuki T, Filion GJ, Deng W, de Dieuleveult M, Fritsch L, Kudithipudi S, Jeltsch A, Leonhardt H, Hajkova P, Marto JA, Arita K, Shinkai Y, Defossez PA. Methylation of dna ligase 1 by g9a/glp recruits uhrf1 to replicating dna and regulates dna methylation. Mol Cell. 2017;67:550-65.
28. Zhang J, Schmit F, Adelmant G, Eck MJ, Marto JA, Zhao JJ, Roberts TM. Crkl is a key regulator of p110beta-dependent pi3k signaling in pten-deficient tumors. Cell Reports 2017;20:549-57.
25. Durzynska I, Xu X, Adelmant G, Ficarro SB, Marto JA, Sliz P, Uljon S, Blacklow SC. Stk40 is a pseudokinase that binds the e3 ubiquitin ligase cop1. Structure 2017;25:287-94.
24. Odajima J, Saini S, Jung P, Ndassa-Colday Y, Ficarro SB, Geng Y, Marco E, Michowski W, Wang YE, Litovchick L, DeCaprio JA, Litovchick L, Marto JA, Sicinski P. Proteomic landscape of tissue-specific cyclin e functions in vivo. PLoS Genetics 2016;12:e1006429.
23. Uljon S, Xu X, Durzynska I, Stein S, Adelmant G, Marto JA, Pear WS, Blacklow SC. Structural basis for substrate selectivity of the e3 ligase cop1. Structure 2016; 24:687-96.
22. Zhang C, Li X, Adelmant G, Dobbins G, Geisen C, Oser M, Wucherpfenning K, Marto JA, Kaelin WG. A peptidic degron in eid1 is recognized by an scf e3 ligase complex containing the orphan f-box protein fbxo21. Proc Natl Acad Sci USA 2015;112:15372-7.
21. Yoda A, Adelmant G, Tamburini J, Chapuy B, Shindoh N, Yoda Y, Weigert O, Kopp N, Wu SC, Card JD, Kim SS, Liu H, Tivey T, Christie AL, Gritsman K, Gotlib J, Deininger MW, Turley S, Tyner JW, Marto JA, Weinstock DM, Lane AA. Mutations in g-protein beta subunits promote transformation and kinase inhibitor resistance. Nat Medicine 2015;21:71-5.
20. Quan J, Adelmant G, Marto JA, Look AT, Yusufzai T. The chromatin remodeling factor chd5 is a transcriptional repressor of wee1. PLoS One 2014;9:e108066.
19. Hill SJ, Rolland T, Adelmant G, Xia X, Owen MS, Dricot A, Zack TI, Sahni N, Jacob Y, Hao T, McKinney KM, Clark AP, Reyon D, Tsai SQ, Joung JK, Beroukhim R, Marto JA, Vidal M, Gaudet S, Hill DE, Livingston DM. Systematic screening reveals a role for brca1 in the response to transcription-associated dna damage. Genes & Dev 2014;28:1957-75.
18. Doherty MF, Adelmant G, Cecchetelli AD, Marto JA, Cram EJ. Proteomic analysis reveals cacn-1 is a component of the splicesome in c. elegans. G3; 2014; 4:1555-64.
17. Meijer DH, Sun Y, Liu T, Kane MF, Alberta JA, Adelmant G, Marto JA, Rowitch D, Nakatani Y, Stiles CD, Mehta S. An amino terminal phosphorylation motif regulates intranuclear compartmentalization of olig2 in neural progenitor cells. J Neuroscience 2014; 34:8507-18.
16. Kim H, Dejsuphong D, Adelmant G, Yang K, Marto JA, D’Andrea AD. A transcriptional repressor zbtb1 is required for uv-induced dna damage tolerance. Mol Cell 2014;54:107-18.
15. Watanabe H, Ma Q, Peng S, Adelmant G, Swain D, Song W, Fox C, Francis JM, Pedamallu CS, DeLuca DS, Brooks AN, Wang S, Que J, Rustgi AK, Wong KK, Ligon KL, Liu XS, Marto JA, Meyerson M, Bass AJ. Sox2-p63 interaction and genomic co-localization in squamous cell carcinomas. J Clin Invest 2014;124:1636-45.
14. Hwang JH, Fernando ATP, Faure N, Andrabi S, Adelmant G, Hahn WC, Marto JA, Shaffhausen BS, Roberts TM. Polyomavirus small t antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol 2014;88:12055-64.
13. Blanke ML, Xu X, Liu H, Ficarro SB, Marto JA, Aster JC, Blacklow SC. Intrinsic selectivity of notch1 for delta-like 4 over delta-like 1. J Biol Chem 2013;288:25477-89.
12. Wang Q, Moore MJ, Adelmant G, Marto JA, Silver PA. PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth. Gene Dev 2013;27:615-26.
11. Fine DA, Rosen OR, Padi M, Korkhin A, James RL, Adelmant G, Yoon R, Guo L, Berrios C, Zhang Y, Calderwood MA, Velmurgan S, Cheng J, Marto JA, Hill DE, Cusick ME, Vidal M, Florens L, Washburn MP, Litovchick L, DeCaprio JA. Identification of fam111a as an sv40 host range restriction factor. PLoS Pathog 2012;8:e1002949.
10. Rosen OR, Deo RC, Padi M, Adelmant GO, Calderwood MA, Pevzner S, Rolland T, Grace M, Dricot A, Askenazi M, Abderazzaq F, Byrdsong D, Chen A, Cheng J, Correll M, Duarte M, Fan C, Ficarro SB, Franchi R, Garg BK, Gulbahce N, Holthaus A, James R, Korkhin A, Litovchick L, Mar JC, Rabello S, Rubio R, Shen Y, Singh S, Spangle JM, Tavares M, Tasan M, Wanamaker S, Webber JT, Carvunis AR, Canfield JR, Johannsen E, Barabasi AL, Beroukhim R, Kieff E, Cusick ME, Hao T, Hill DE, Munger K, Marto JA*, Quackenbush J*, Roth FP*, DeCaprio JA*, Vidal M*. Interpreting cancer genomes using systematic host perturbations by tumour virus proteins. Nature 2012;487:491-5.
9. Adelmant G, Calkins AS, Garg BK, Card JD, Askenazi M, Miron A, Sobhian B, Zhang Y, Nakatani Y, Silver PA, Iglehart JD, Marto JA*, Lazaro JB*. DNA ends alter the molecular composition and localization of ku mult-component complexes. Mol Cell Proteomics 2012;11:411-21.
8. Gulbahce N, Yan H, Dricot A, Byrdsong D, Franchi R, Lee DS, Calderwood MA, Santhanam B, Braun P, Huh KW, Mar JC, Baldwin A, Zhao B, Hellner K, Grace M, Padi M, Rubio R, Marto JA, Quackenbush J, DeCaprio JA, Christakis NA, Kieff E, Roth FP, Munger K, Roecklein-Canfield J, Cusick ME, Hill DE, Vidal M, Barabasi AL. Viral perturbations of host networks reflect disease etiology. PLoS Comp Biol 2012;8:e1002531.
7. Koleva RI, Ficarro SB, Radomska HS, Alfonso MC, Webber JT, Luckey CJ, Marcucci G, Tenen DG, Marto JA. C/ebp-alpha and dek coordinately regulate myeloid differentiation. Blood 2012;119:4878-4888.
6. Pathania S, Nguyen J, Hill SJ, Scully R, Adelmant GO, Marto JA, Feunteun J, Livingston DM. BRCA1 is required for post-replication repair after uv-induced dna damage, Mol Cell 2011;44:235-51.
5. Odajima J, Wills ZP, Ndassa-Colday YM, Terunuma M, Kretschmannova, K, Deeb TZ, Geng Y, Gawrzak S, Quadros IM, Newman J, Das M, Jecrois ME, Li N, Bienvenu F, Moss SJ, Greenberg ME, Marto JA*, Sicinski P*. Cycin E constains cdk5 activity to regulate synaptic plasticity and memory formation, Dev Cell 2011;21:655-68§.
4. Dejmek JS, Adelmant GO, Sobhian B, Calkins AS, Marto JA, Iglehart JD, Lazaro JB. Concordant and opposite roles of dna-pk and the facilitator of chromatin transcription (fact) in dna repair, apoptosis and necrosis after cisplatin. Mol Cancer 2011;10:74.
3. Meixner A, Boldt K, Troys MV, Askenazi M, Gloeckner CJ, Bauer M, Marto JA, Ampe C, Kinkl N, Ueffing M. A quick screen for lrrk2 interaction partners – leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics. Mol Cell Proteomics 2011;10:M110.001172 1-17.
2. Chen Z, Sasaki T, Tan X, Carretero J, Shimamura T, Li Danan, Xu C, Wang Y, Adelmant GO, Capelletti M, Lee HJ, Rodig S, Borgman C, Park S, Kim HR, Padera R, Marto JA, Gray NS, Kung AL, Shapiro GI, Janne PA, Wong KK. Inhibition of alk, pi3k/mek and hsp90 in murine lung adenocarcinoma induced by eml4-alk fusion oncogene. Cancer Res 2010;70:9827-36.
1. Simarro M, Cassina AG, Kedersha N, Lazaro JB, Adelmant GO, Marto JA, Rhee K, Tisdale S, Danial N, Benarafa C, Orduna A, Anderson P. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration. Biochem Biophys Res Commun 2010;401:440-6.