Leonore Novak

Dottoressa di ricerca

ciclo: XXXIV

supervisore: Roberta Chiaraluce

Titolo della tesi: Impact of ERK2 missense variants found in cancer: structural, function and stability experimental analysis

The extracellular-signal-regulated kinase (ERK2) participates in the Ras-Raf-MEK-ERK signal transduction cascade involved in the regulation of a large variety of cellular processes. ERK2 is the principal effector of a central signaling cascade that converts extracellular stimuli into cell proliferation and migration responses and, when deregulated, can promote cell oncogenic transformation. The deviation from the strict control of ERK2 signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and various types of cancers. Several ERK2 variants have been identified in cancer tissues as nonsynonymous single nucleotide variants (nsSNVs) that occur in the DNA coding region and encode a change in the amino acid sequence. This thesis reports the collection of structural, function and stability data of unphosphorylated (NP-) and phosphorylated (P-)ERK2 wild type and 17 somatic variants. A detailed understanding of the changes of the investigated gene products, at the molecular level, to assess how genetic variations impact the protein folding, structure, functions, and interactions is required to develop new therapeutic strategies, particularly in the search of small molecules able to selectively interact with the variants: that is an essential preliminary step to personalized medicine, and help to identify new potential therapeutic targets.

Produzione scientifica

11573/1703621 - 2024 - Critical assessment of genome interpretation consortium. CAGI, the critical assessment of genome interpretation, establishes progress and pprospects for computational genetic variant interpretation methods.

Jain, Shantanu; Bakolitsa, Constantina; E Brenner, Steven; Radivojac, Predrag; Moult, John; Repo, Susanna; A Hoskins, Roger; Andreoletti, Gaia; Barsky, Daniel; Chellapan, Ajithavalli; Chu, Hoyin; Dabbiru, Navya; K Kollipara, Naveen; Ly, Melissa; J Neumann, Andrew; R Pal, Lipika; Odell, Eric; Pandey, Gaurav; C Peters-Petrulewicz, Robin; Srinivasan, Rajgopal; F Yee, Stephen; Jyothsna Yeleswarapu, Sri; Zuhl, Maya; Adebali, Ogun; Patra, Ayoti; A Beer, Michael; Hosur, Raghavendra; Peng, Jian; M Bernard, Brady; Berry, Michael; Dong, Shengcheng; P Boyle, Alan; Adhikari, Aashish; Chen, Jingqi; Hu, Zhiqiang; Wang, Robert; Wang, Yaqiong; Miller, Maximilian; Wang, Yanran; Bromberg, Yana; Turina, Paola; Capriotti, Emidio; J Han, James; Ozturk, Kivilcim; Carter, Hannah; Babbi, Giulia; Bovo, Samuele; Di Lena, Pietro; Luigi Martelli, Pier; Savojardo, Castrense; Casadio, Rita; S Cline, Melissa; De Baets, Greet; Bonache, Sandra; Díez, Orland; Gutiérrez-Enríquez, Sara; Fernández, Alejandro; Montalban, Gemma; Ootes, Lars; Özkan, Selen; Padilla, Natàlia; Riera, Casandra; De La Cruz, Xavier; Diekhans, Mark; J Huwe, Peter; Wei, Qiong; Xu, Qifang; L Dunbrack, Roland; Gotea, Valer; Elnitski, Laura; Margolin, Gennady; Fariselli, Piero; V Kulakovskiy, Ivan; J Makeev, Vsevolod; D Penzar, Dmitry; E Vorontsov, Ilya; V Favorov, Alexander; R Forman, Julia; Hasenahuer, Marcia; S Fornasari, Maria; Parisi, Gustavo; Avsec, Ziga; H Çelik, Muhammed; Yen Duong Nguyen, Thi; Gagneur, Julien; Shi, Fang-Yuan; D Edwards, Matthew; Guo, Yuchun; Tian, Kevin; Zeng, Haoyang; K Gifford, David; Göke, Jonathan; Zaucha, Jan; Gough, Julian; S Ritchie, Graham R; Frankish, Adam; M Mudge, Jonathan; Harrow, Jennifer; L Young, Erin; Yu, Yao; D Huff, Chad; Murakami, Katsuhiko; Nagai, Yoko; Imanishi, Tadashi; J Mungall, Christopher; B Jacobsen, Julius O; Kim, Dongsup; Jeong, Chan-Seok; T Jones, David; Jun Li, Mulin; Beleva Guthrie, Violeta; Bhattacharya, Rohit; Chen, Yun-Ching; Douville, Christopher; Fan, Jean; Kim, Dewey; Masica, David; Niknafs, Noushin; Sengupta, Sohini; Tokheim, Collin; N Turner, Tychele; Ting Grace Yeo, Hui; Karchin, Rachel; Shin, Sunyoung; Welch, Rene; Keles, Sunduz; Li, Yue; Kellis, Manolis; Corbi-Verge, Carles; V Strokach, Alexey; M Kim, Philip; E Klein, Teri; Mohan, Rahul; A Sinnott-Armstrong, Nicholas; Wainberg, Michael; Kundaje, Anshul; Gonzaludo, Nina; Y Mak, Angel C; Chhibber, Aparna; K Lam, Hugo Y; Dahary, Dvir; Fishilevich, Simon; Lancet, Doron; Lee, Insuk; Bachman, Benjamin; Katsonis, Panagiotis; C Lua, Rhonald; J Wilson, Stephen; Lichtarge, Olivier; R Bhat, Rajendra; Sundaram, Laksshman; Viswanath, Vivek; Bellazzi, Riccardo; Nicora, Giovanna; Rizzo, Ettore; Limongelli, Ivan; M Mezlini, Aziz; Chang, Ray; Kim, Serra; Lai, Carmen; O'connor, Robert; Topper, Scott; Van Den Akker, Jeroen; Y Zhou, Alicia; D Zimmer, Anjali; Mishne, Gilad; R Bergquist, Timothy; R Breese, Marcus; F Guerrero, Rafael; Jiang, Yuxiang; Kiga, Nikki; Li, Biao; Mort, Matthew; A Pagel, Kymberleigh; Pejaver, Vikas; H Stamboulian, Moses; Thusberg, Janita; D Mooney, Sean; Teerakulkittipong, Nuttinee; Cao, Chen; Kundu, Kunal; Yin, Yizhou; Yu, Chen-Hsin; Kleyman, Michael; Lin, Chiao-Feng; Stackpole, Mary; M Mount, Stephen; Eraslan, Gökcen; S Mueller, Nikola; Naito, Tatsuhiko; R Rao, Aliz; R Azaria, Johnathan; Brodie, Aharon; Ofran, Yanay; Garg, Aditi; Pal, Debnath; Hawkins-Hooker, Alex; Kenlay, Henry; Reid, John; J Mucaki, Eliseos; K Rogan, Peter; M Schwarz, Jana; B Searls, David; Rie Lee, Gyu; Seok, Chaok; Krämer, Andreas; Shah, Sohela; V Huang, Chenglai; F Kirsch, Jack; Shatsky, Maxim; Cao, Yue; Chen, Haoran; Karimi, Mostafa; Moronfoye, Oluwaseyi; Sun, Yuanfei; Shen, Yang; Shigeta, Ron; T Ford, Colby; Nodzak, Conor; Uppal, Aneeta; Shi, Xinghua; Joseph, Thomas; Kotte, Sujatha; Rana, Sadhna; Rao, Aditya; G Saipradeep, V; Sivadasan, Naveen; Sunderam, Uma; Stanke, Mario; Su, Andrew; Adzhubey, Ivan; M Jordan, Daniel; Sunyaev, Shamil; Rousseau, Fr - 01a Articolo in rivista

rivista: GENOME BIOLOGY (BioMed Central) pp. 1-46 - issn: 1474-760X - wos: WOS:001184832400002 (7) - scopus: 2-s2.0-85187866396 (10)

11573/1687882 - 2023 - Mutation in the common docking domain affects MAP kinase ERK2 catalysis and stability

Novak, L.; Petrosino, M.; Pasquo, A.; Chaikuad, A.; Chiaraluce, R.; Knapp, S.; Consalvi, V. - 01a Articolo in rivista

rivista: CANCERS (Basel: MDPI) pp. 2938- - issn: 2072-6694 - wos: WOS:001005128700001 (2) - scopus: 2-s2.0-85161439953 (2)

11573/1691038 - 2023 - The complex impact of cancer‑related missense mutations on the stability and on the biophysical and biochemical properties of MAPK1 and MAPK3 somatic variants

Petrosino, M; Novak, L; Pasquo, A; Turina, P; Capriotti, E; Minicozzi, V; Consalvi, V; Chiaraluce, R - 01a Articolo in rivista

rivista: HUMAN GENOMICS (BioMed Central Ltd Part of Springer Nature. London: Henry Stewart Publications) pp. 1-23 - issn: 1479-7364 - wos: WOS:001092692600001 (0) - scopus: 2-s2.0-85175098011 (0)

11573/1639927 - 2022 - Metal ion binding in wild-type and mutated frataxin: a stability study

Morante, S; Botticelli, S; Chiaraluce, R; Consalvi, V; La Penna, G; Novak, L; Pasquo, A; Petrosino, M; Proux, O; Rossi, G; Salina, G And Stellato F - 01a Articolo in rivista

rivista: FRONTIERS IN MOLECULAR BIOSCIENCES (Lausanne : Frontiers Media S.A., 2014-) pp. - - issn: 2296-889X - wos: WOS:000810933200001 (0) - scopus: 2-s2.0-85132388442 (0)

11573/1549781 - 2021 - A glimpse into the structural properties of the intermediate and transition state in the folding of bromodomain 2 d2 by Φ value analysis

Novak, Leonore; Petrosino, Maria; Santorelli, Daniele; Chiaraluce, Roberta; Consalvi, Valerio; Pasquo, Alessandra; Travaglini-Allocatelli, Carlo - 01a Articolo in rivista

rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 5953- - issn: 1422-0067 - wos: WOS:000660211300001 (1) - scopus: 2-s2.0-85106937341 (1)

11573/1548711 - 2021 - Analysis and interpretation of the impact of missense variants in cancer

Petrosino, M.; Novak, L.; Pasquo, A.; Chiaraluce, R.; Turina, P.; Capriotti, E.; Consalvi, V - 01g Articolo di rassegna (Review)

rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. - - issn: 1422-0067 - wos: WOS:000660133900001 (33) - scopus: 2-s2.0-85106316558 (36)

11573/1277788 - 2019 - Characterization of human frataxin missense variants in cancer tissues

Petrosino, Maria; Pasquo, Alessandra; Novak, Leonore; Toto, Angelo; Gianni, Stefano; Mantuano, Elide; Veneziano, Liana; Minicozzi, Velia; Pastore, Annalisa; Puglisi, Rita; Capriotti, Emidio; Chiaraluce, Roberta; Consalvi, Valerio - 01a Articolo in rivista

rivista: HUMAN MUTATION (John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551) pp. 1-14 - issn: 1059-7794 - wos: WOS:000485994200020 (14) - scopus: 2-s2.0-85070717849 (16)