Glickman - פקולטה לביולוגיה Biology Faculty

Education/ Resume:

PhD, University of California, Berkeley, 1994
BSc, Hebrew University, Jerusalem, 1989

Research Summary

Protein Turnover in Alzheimer’s disease, ageing and response to mitochondria dysfunction. We have a long-standing interest in understanding how ubiquitin and ubiquitin-like signals are recognized at the proteasome and the corresponding features of proteasome structure and function that define it as a molecular machine for intracellular protein degradation. We have adapted a 3-D human neuronal network to study the role of proteasome, deubiquitinating enzymes and ubiquitin signaling in general in neurodegeneration.

Awards:

2013-2014 Bessel Research Award, Humboldt Foundation, Germany
2012 Deutsche Technion-Gesellschaft Prize (with Dr. Thomas Sommer /MDC)

Key Publications:

Glickman MH, Rubin DM, Coux O, Wefes I, Pfeifer G, Cjeka Z, Baumeister W, Fried VA, Finley D.A subcomplex of the regulatory particle of the proteasome necessary for ubiquitin-conjugate degradation and related to the COP9/Signalosome and eIF3. Cell 1998 (94) 615-623.
Glickman, M.H., Ciechanover, A. The Ubiquitin-proteasome Proteolytic Pathway: Destruction for the sake of construction, Physiological Reviews 2002 (82) 373-428.

Matiuhin Y., Kirkpatrick D.S., Ziv I., Kim W., Dakshinamurthy A., Kleifeld O., Gygi S.P., Reis N., Glickman M.H. Extraproteasomal Rpn10 restricts access of the polyubiquitin-binding protein Dsk2 to proteasome, Mol. Cell 2008 (32), 415-425
ZhangD., ChenT., ZivI., Rosenzweig R., Matiuhin Y., Bronner V., Lee S., Glickman M.H*, and Fushman D*. Together Rpn10 and Dsk2 serve as a polyubiquitin chain-length sensor. Mol. Cell, 2009 (36) 1018-1033.
Ziv I, Matiuhin Y, Kirkpatrick DS, Erpapazoglou Z, Leon S, Pantazopoulou M, Kim W, Gygi SP, Haguenauer-Tsapis R, Reis N, Glickman MH^*, Kleifeld O^*, A perturbed ubiquitin landscape distinguishes between ubiquitin in trafficking and in proteolysis.,Mol Cell Proteomics. 2011 May;10(5):M111.009753.
Krutauz D, Reis N, Nakasone MA, Siman P, Zhang D, Kirkpatrick DS, Gygi SP, Brik A, Fushman D, Glickman MH. Extended ubiquitin species are protein-based DUB inhibitors. Nature Chemical Biology 2014 Aug;10(8):664-70
Livnat-Levanon N, Kevei É, Kleifeld O, Krutauz D, Segref A, Rinaldi T, Erpapazoglou Z, Cohen M, Reis N, Hoppe T, Glickman MH. Reversible 26S proteasome disassembly upon mitochondrial stress. Cell Reports. 2014 Jun 12;7(5):1371-80
Sumeet K. Singh, Indrajit Sahu, Sachitanand M. Mali, Hosahalli P. Hemantha, Oded Kliefeld, Michael H. Glickman*, and Ashraf Brik*, Synthetic Uncleavable Ubiquitinated Proteins Dissect Proteasome Deubiquitination and Degradation, and Highlight Distinctive Fate of Tetraubiquitin, J. Am. Chem. Soc., December 6, 2016 (Article)DOI: 10.1021/jacs.6b09611
Michal Chojnacki, Wissam Mansour, Dharjath S. Hameed, Rajesh Singh, Rina Rosenzweig, Mark A. Nakasone, Farid El Oualid, Zanlin Yu, Fabian Glaser, Lewis E. Kay, David Fushman, HuibOvaa and Michael H. Glickman1*, Polyubiquitin-Photoactivatable CrosslinkingReagents for Mapping Ubiquitin Interactome IdentifyRpn1 as a Proteasome Ubiquitin-Associating Subunit, Cell Chemical Biology 201724, 1–15 April 20,http://dx.doi.org/10.1016/j.chembiol.2017.02.013
Ding Z, Xu C, Sahu I, Wang Y, Fu Z, Huang M, Wong CCL, Glickman MH, Cong Y.Structural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations.Mol Cell. 2019 Feb 12. pii: S1097-2765(19)30038-3. doi: 10.1016/j.molcel.2019.01.018

Recent Publications:

Mark A. Nakasone, Timothy A. Lewis, Olivier Walker, Anita Thakur, Wissam Mansour, Carlos A. Castañeda, Jennifer L. Goeckeler-Fried, Frank Parlati, Tsui-Fen Chou, Ortal Hayat, Urszula K. Nowicka1, Susan Krueger, Michael H. Glickman, Jeffrey L. Brodsky, Raymond J. Deshaies, and David Fushman, Structural basis for the inhibitory effects of ubistatins in the ubiquitin-proteasome pathway, Structure. 2017 Dec 5;25(12):1839-1855.e11

Bramasole L, Sinha A, Gurevich S, Radzinski M, Klein Y, Panat N, Gefen E, Rinaldi T, Jimenez-Morales D, Johnson J, Krogan NJ, Reis N, Reichmann D, Glickman MH, Pick E.Proteasome lid bridges mitochondrial stress with Cdc53/Cullin1 NEDDylation status.Redox Biol. 2019 Jan;20:533-543. doi: 10.1016/j.redox.2018.11.010. Epub 2018 Nov 17.
Ding Z, Xu C, Sahu I, Wang Y, Fu Z, Huang M, Wong CCL, Glickman MH, Cong Y.Structural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations.Mol Cell. 2019 Feb 12. pii: S1097-2765(19)30038-3. doi: 10.1016/j.molcel.2019.01.018
Bramasole L, Sinha A, Harshuk D, Cirigliano A, Gurevich S, Yu Z, Carmeli RL, Glickman MH, Rinaldi T, Pick E. The Proteasome Lid Triggers COP9 Signalosome Activity during the Transition of Sachharomyces cerevisiae Cells into Quiescence. Biomolecules. 2019 Sep 4;9(9). pii: E449. doi: 10.3390/biom9090449.
Prasad Sulkshane, Inbar Duek, Jonathan Ram, Anita Thakur, Noa Reis, Tamar Ziv, and Michael H Glickman, Inhibition of proteasome reveals basal mitochondrial ubiquitinationInhibition of proteasome reveals basal mitochondrial ubiquitination.Sulkshane P, Duek I, Ram J, Thakur A, Reis N, Ziv T, Glickman MH.J Proteomics. 2020 Oct 30;229:103949. doi: 10.1016/j.jprot.2020.103949. PMID: 32882436
Vamisetti, G. B., Gandhesiri, S., Sulkshane, P., Mann, G., Glickman, M. H., andBrik, A. (2020). On-Demand Detachment of Maleimide Derivatives on Cysteine to Facilitate (Semi)Synthesis of Challenging Proteins. J Am Chem. Soc. 2020 142(46):19558-19569
Sulkshane P, and Glickman MH., Proteasome participation in mitochondria-associated degradationBiomolecules. 2020 10(11):1559. doi: 10.3390/biom10111559.
Sylvia ZerathGurevich, Abhishek Sinha, Joseph Longworth, Rajesh K. Singh, Betsegaw Lemma, Anita Thakur, Oliver Popp, Daniel Kornitzer, Noa Reis, Gunnar Dittmar, Elah Pick, David Fushman, Michael H. Glickman.Rub1/NEDD8, a ubiquitin-like modifier, is also a ubiquitin modifier (under revision at J. Biol. Chem.) bioRxiv 2020.06.18.159145; doi: 10.1101/2020.06.18.159145
Indrajit Sahu, Sachitanand M. Mali, Prasad Sulkshane, Andrey Rozenberg, Cong Xu, Roni Morag, Manisha PriyadarsiniSahoo, Sumeet K. Singh, Zhanyu Ding, Yifan Wang, Sharleen Day, Yao Cong, Oded Kleifeld, Ashraf Brik, Michael H. Glickman, Signature activities of 20S proteasome include degradation of the ubiquitin-tag with the protein under hypoxiadoi: https://doi.org/10.1101/2019.12.20.883942 (under revision)

Michael Glickman, head of the Lab for Protein Characterization at the Faculty of Biology, Technion

Could you imagine if nothing is thrown out, yet never recycled? Garbage would pile up until the clutter would be devastating. That is what happens in cells; all proteins are continuously broken down and recycled into amino acids, and rebuilt as needed. By studying protein recycling we uncover how cells combat aging. As we get older, the system for protein quality assurance in our bodies becomes frail.