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450 West Drive
Chapel Hill, NC

University of North Carolina, Chapel Hill

The Emanuele Lab studies cell cycle regulation using systematic technologies and traditional cell, molecular and biochemical techniques.

Publications

** indicates corresponding author publications

2024

**Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases. Bolhuis DL, Emanuele MJ, Brown NG. Biochem Soc Trans. 2024 Feb 28:BST20230454. doi: 10.1042/BST20230454. Online ahead of print. PMID: 38414432

2023

**Proteomic Analysis Reveals a PLK1-Dependent G2/M Degradation Program and Links PKA-AKAP2 to Cell Cycle Control. Mouery RD, Hsu C, Bonacci T, Bolhuis DL, Wang X, Mills CA, Toomer ED, Canterbury OG, Robertson KC, Branigan TB, Brown NG, Herring LE, Emanuele MJ. bioRxiv [Preprint]. 2023 Oct 12:2023.10.11.561963. doi: 10.1101/2023.10.11.561963. PMID: 37873169

Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C). Bodrug T, Welsh KA, Bolhuis DL, Paulаkonis E, Martinez-Chacin RC, Liu B, Pinkin N, Bonacci T, Cui L, Xu P, Roscow O, Amann SJ, Grishkovskaya I, Emanuele MJ, Harrison JS, Steimel JP, Hahn KM, Zhang W, Zhong ED, Haselbach D, Brown NG. Nat Struct Mol Biol. 2023 Nov;30(11):1663-1674. doi: 10.1038/s41594-023-01105-5. Epub 2023 Sep 21. PMID: 37735619

Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer. Huang Y, Fan Y, Zhao Z, Zhang X, Tucker K, Staley A, Suo H, Sun W, Shen X, Deng B, Pierce SR, West L, Yin Y, Emanuele MJ, Zhou C, Bae-Jump V. Int J Mol Sci. 2023 Aug 3;24(15):12375. doi: 10.3390/ijms241512375. PMID: 37569750

AtomNet-Aided OTUD7B Inhibitor Discovery and Validation. Chen J, Bolhuis DL, Laggner C, Kong D, Yu L, Wang X, Emanuele MJ, Brown NG, Liu P. Cancers (Basel). 2023 Jan 14;15(2):517. doi: 10.3390/cancers15020517. PMID: 36672466

Enabling Genetic Code Expansion and Peptide Macrocyclization in mRNA Display via a Promiscuous Orthogonal Aminoacyl-tRNA Synthetase. Iskandar SE, Pelton JM, Wick ET, Bolhuis DL, Baldwin AS, Emanuele MJ, Brown NG, Bowers AA. J Am Chem Soc. 2023 Jan 11. doi: 10.1021/jacs.2c11294.

2022

Examining the mechanistic relationship of APC/CCDH1 and its interphase inhibitor EMI1. Bolhuis DL, Martinez-Chacin RC, Welsh KA, Bodrug T, Cui L, Emanuele MJ, Brown NG. Protein Science. 2022 Jun;31(6):e4324. PMID: 35634770

Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes. Welsh KA, Bolhuis DL, Nederstigt AE, Boyer J, Temple BRS, Bonacci T, Gu L, Ordureau A, Harper JW, Steimel JP, Zhang Q, Emanuele MJ, Harrison JS, Brown NG. EMBO J. 2022 Feb 1;41(3):e108823. PMID: 34942047

2021

** Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2. Enrico TP, Stallaert W, Wick ET, Ngoi P, Wang X Rubin SM, Brown NB, Purvis JE, Emanuele MJ. Elife. 2021 Dec 1;10:e70691. doi: 10.7554/eLife.70691. PMID: 34851822.

Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation. Bodrug T, Welsh KA, Hinkle M, Emanuele MJ, Brown NG. Front Cell Dev Biol. 2021 May 24;9:687515. doi: 10.3389/fcell.2021.687515. eCollection 2021.

Elucidating Human Mitosis Using an Anaphase-Like Cell-Free System. Wasserman D, Nachum S, Noach-Hirsh M, Auerbach N, Sheinberger-Chorni E, Enrico TP, Lahmi R, Emanuele MJ, Tzur A. Methods in Molecular Biology. 2021;2329:143-164.

** Sirtuin 5 is Regulated by the SCF-Cyclin F Ubiquitin Ligase and is Involved in Cell Cycle Control. Mills CA, Wang X, Bhatt DP, Grimsrud PA, Matson JP, Lahiri D, Burke DJ, Cook JG, Hirschey MD, Emanuele MJ. Molecular and Cellular Biology. 2021 Jan 25;41(2):e00269-20.


2020

** In silico APC/C substrate discovery reveals cell cycle degradation of chromatin regulators including UHRF1. Franks JL, Martinez-Chacin RC, Wang X, Tiedemann RL, Bonacci T, Choudhury R, Bolhuis D, Damrauer JS, Yan F, Harrison JS, Major MB, Hoadley K, Suzuki A, Rothbart SB, Brown NG, Emanuele MJ. PLOS Biology. 2020 Dec 11;18(12):e3000975.

Thiopeptides Induce Proteasome-Independent Activation of Cellular Mitophagy. Bird KE, Xander C,  Murcia S, Schmalstig AA, Wang X, Emanuele MJ, Braunstein M, Bowers AA. ACS Chemical Biology. 2020 Aug 21;15(8):2164-2174.

** Complex cartography: E2F transcriptional control by Cyclin F and ubiquitin. Emanuele MJ, Enrico TP, Mouery R, Wasserman S, Nachum S, Tzur A. Trends in Cell Biology. 2020 Aug;30(8):640-652.

** Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming. Martinez-Chacin RC, Bodrug T, Bolhuis DL, Kedziora KM, Bonacci T, Ordureau A, Gibbs ME, Weissmann F, Qiao R, Grant GD, Cook JG, Peters JM, Wade Harper J, Emanuele MJ, Brown NG.Nat Struct Mol Biol. 2020 Jun;27(6):550-560.

** Dissenting degradation: Deubiquitinases in cell cycle and cancer. Bonacci T, Emanuele MJ. Seminars in Cancer Biology. 2020 Mar 20:S1044-579X(20)30066-3.

Cell cycle oscillators underlying orderly proteolysis of E2F8. Wasserman D, Nachum S, Cohen M, Enrico TP, Noach-Hirsh M, Parasol J, Zomer-Polak S, Auerbach N, Sheinberger-Chorni E, Nevenzal H, Levi-Dadon N, Wang X, Lahmi R, Michaely E, Gerber D, Emanuele MJ, Tzur A. Molecular Biology of the Cell. 2020 Apr 1;31(8):725-740.

Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells. McDonald IM, Grant GD, East MP, Gilbert TS, Wilkerson EM, Goldfarb D, Beri J, Herring LE, Vaziri C, Cook JG, Emanuele MJ, Graves LM. Journal of Biological Chemistry. 2020 Feb 21;295(8):2359-2374.


2019

Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer. Blake DR, Vaseva AV, Hodge RG, Kline MP, Gilbert TSK, Tyagi V, Huang D, Whiten GC, Larson JE, Wang X, Pearce KH, Herring LE, Graves LM, Frye SV, Emanuele MJ, Cox AD, Der CJ. Science Signaling. 2019 Jul 16;12(590).

** Impressionist portraits of mitotic exit: APC/C, K11-linked ubiquitin chains and Cezanne. Bonacci T, Emanuele MJ. Cell Cycle. 2019 Mar-Apr;18(6-7):652-660.

** FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal-Like Breast Cancer. Arceci A, Bonacci T, Wang X, Stewart K, Damrauer JS, Hoadley KA, Emanuele MJ. Cell Reports. 2019 Mar 12;26(11):3076-3086.e6.

** Ubiquitin Signaling in Regulation of the Start of the Cell Cycle. Emanuele MJ, Enrico TP. Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease (Book Chapter). Intech Open. 2019 Jan 10.


2018

** Who guards the guardian? Mechanisms that restrain APC/C during the cell cycle. Kernan J, Bonacci T, Emanuele MJ. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2018 Dec;1865(12):1924-1933. 

** Cezanne/OTUD7B is a cell cycle-regulated deubiquitinase that antagonizes the degradation of APC/C substrates. Bonacci T, Suzuki A, Grant GD, Stanley N, Cook JG, Brown NG, Emanuele MJ. EMBO Journal. 2018 Aug 15;37(16):e98701.

Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity. Dronamraju R, Jha DK, Eser U, Adams AT, Dominguez D, Choudhury R, Chiang YC, Rathmell WK, Emanuele MJ, Churchman LS, Strahl BD. Nucleic Acids Research. 2018 Feb 16;46(3):1331-1344.

Self-oligomerization regulates stability of Survival Motor Neuron (SMN) protein isoforms by sequestering an SCFSlmb degron. Gray KM, Kaifer KA, Baillat D, Wen Y, Bonacci TR, Ebert AD, Raimer AC, Spring AM, Have ST, Glascock JJ, Gupta K, Van Duyne GD, Emanuele MJ, Lamond AI, Wagner EJ, Lorson CL, Matera AG. Molecular Biology of the Cell. 2018 Jan 15;29(2):96-110.


2017

** Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation. Mills CA, Suzuki A, Arceci A, Mo JY, Duncan A, Salmon ED, Emanuele MJ. Journal of Biological Chemistry. 2017 Oct 20;292(42):17178-17189.

** The E3 ubiquitin ligase SCF(Cyclin F) transmits AKT signaling to the cell cycle machinery. Choudhury R, Bonacci T, Wang W, Truong A, Arceci A, Zhang Y, Mills, CA, Kernan JL, Liu P, Emanuele MJ. Cell Reports. 2017 Sep 26;20(13):3212-3222.

 The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/β-catenin pathway by inhibiting the proteasome. Yi JJ, Paranjape SR, Walker MP, Choudhury R, Wolter JM, Fragola G, Emanuele MJ, Major MB, Zylka MJ. Journal of Biological Chemistry. 2017 Jul 28;292(30):12503-12515. doi: 10.1074/jbc.M117.788448.

** VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1. Wang X, Arceci A, Bird K, Mills CA, Choudhury R, Kernan JL, Zhou C, Bae-Jump V, Bowers A, Emanuele MJ. Molecular and Cellular Biology. 2017 Jun 15;37(13). pii: e00609-16. doi: 10.1128/MCB.00609-16.

 

2016

** APC/C and SCF(cyclin F) constitute a reciprocal feedback circuit controlling S-phase entry. Choudhury C, Bonacci T, Arceci A,  Lahiri D, Mills CA, Kernan JL, Branigan TB, DeCaprio JA, Burke D, Emanuele MJ. Cell Reports. 2016 Sep 20;16(12):3359-72.


2014

SNF5/INI1 Deficiency Redefines Chromatin Remodeling Complex Composition During Tumor Development.  Wei D, Goldfarb D, Song S, Cannon C, Sakellariou-Thompson D, Emanuele M, Major MB, Weissman BE and Kuwahara Y. Molecular Cancer Research. 2014 Nov;12(11):1574-85.

 A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells. Ly T, Ahmad Y, Shlien A, Soroka D, Mills A, Emanuele MJ, Stratton MR, Lamond AI. eLife 2014;3:e01630.

Chlamydia trachomatis-Induced Alterations in the Host Cell Proteome Are Required for Intracellular Growth. Olive AJ, Haff MG, Emanuele MJ, Sack LM, Barker JR., Elledge SJ, Starnbach MN. Cell Host Microbe. 2014 Jan 15; 15(1):113-24.

Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells. Weng MT, Lee JH, Wei SC, Li Q, Shahamatdar S, Hsu D, Schetter AJ, Swatkoski S, Mannan P, Garfield S, Gucek M, Kim MK, Annunziata CM, Creighton CJ, Emanuele MJ, Harris CC, Sheu JC, Giaccone G, Luo J. PNAS. 2012 Dec 26; 109(52):E3659-67.


Pre-2013

Global Identification of Modular Cullin-Ring Ligase Substrates. Emanuele MJ, Elia EH, Xu Q, Thoma CR, Izhar L, Guo A, Rush J, Hsu PW, Yen HS, Elledge SJ. Cell. 2011 Oct 14;147(2):459-74. 

 Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate. Emanuele MJ, Ciccia A, Elia AE, Elledge SJ. PNAS. 2011 108 (24) 9845-9850.

 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong K, Elledge SJ. Cell. 2009 May 29; 137(5). 835-48.

 Probing Kinetochore Structure and Function Using Xenopus laevis Frog Egg Extracts. Emanuele MJ and Stukenberg PT.  Methods in Molecular Biology.  2009; 545:221-32. (Methods Chapter)

 Aurora B kinase and Protein Phosphatase 1 have opposing roles in modulating kinetochore assembly. Emanuele MJ, Lan W, Jwa M, Miller SA, Chan, CSM, Stukenberg PT.  J Cell Biol. 2008 Apr 21; 181(2):241-54.

 Multiple mechanisms of chromosome movement mediated through the Ndc80 complex and Dynein/Dynactin. Vorozko VV, Emanuele MJ, Kallio MJ, Stukenberg PT, Gorbsky GJ. Chromosoma. 2008 Apr; 117(2):169-79.

 Xenopus Cep57 is a novel kinetochore component involved in microtubule attachment. Emanuele MJ and Stukenberg PT.   Cell. 2007 Sep 7; 130(5):893-905. 

 A Hec of a microtubule attachment.  Emanuele M, Burke DJ, Stukenberg PT. Nature Structural and Molecular Biology. 2007 Jan; 14(1):11-3. (news and views)

Measuring the stoichiometry and physical interactions between components elucidates the architecture of the vertebrate kinetochore. Emanuele MJ, McCleland ML, Satinover DL, Stukenberg PT.  Mol Biol Cell. 2005 Oct; 16(10):4882-92.

Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome. Wang HW, Putt ME, Emanuele MJ, Shin DB, Glatstein E, Yodh AG, Busch TM.   Cancer Res. 2004 Oct 15; 64(20):7553-61.

 Hypoxia and Photofrin uptake in the intraperitoneal carcinomatosis and sarcomatosis of photodynamic therapy patients. Busch TM, Hahn SM, Wileyto EP, Koch CJ, Fraker DL, Zhang P, Putt M, Gleason K, Shin DB, Emanuele MJ, Jenkins K, Glatstein E, Evans SM.   Clin Cancer Res. 2004 Jul 15; 10(14):4630-8.

 Photodynamic therapy creates fluence rate-dependent gradients in the intratumoral spatial distribution of oxygen. Busch TM, Wileyto EP, Emanuele MJ, Del Piero F, Marconato L, Glatstein E, Koch CJ. Cancer Res. 2002 Dec 15; 62(24):7273-9.