Dr. Elah Pick
The Klein Center for Molecular and Environmental Biology
Department of Biology and Environment, Faculty of Natural Sciences
University of Haifa at Oranim, 36006 Tivon, Israel
Office: (972) 4 9838988
Lab: (972) 4 9838985
Fax: (972) 4 9539608
The focus of research in our lab is on studies of the mechanisms and evolutionary conservation of quality-control regulators among the family of PCI protein complexes. The budding yeast Saccharomyces cerevisiae is the main model system used in our studies.
Paralog PCI complexes – the proteasome lid, the COP9 signalosome (CSN) and the eukaryotic initiation factor-3 (eIF3), have diverged from a common ancestor, yet fulfilling separate and distinctive functions. Orthologs of all their subunits are highly conserved among multicellular organisms (figure 1), however in some fungi, and particularly in S. cerevisiae, only the proteasome lid bears a canonical composition (Figure 2, table 1). In the two other PCI complexes, (eIF3 and CSN) only a subset of core-subunits has been positively identified. This raises the question: how do these complexes carry out their functions while lacking core subunits? Extreme divergence of subunits may account for some apparently "missing" subunits; i.e. they are not truly absent but are simply hard to identify by bioinformatics alone. In a recent study (Yu et al. 2011), we found that—at least in budding yeast, one of the proteasome lid subunits, Rpn5, took-over the role of a paralog CSN subunit, and is now multi-tasking independently in both, CSN and the lid. This is the first example for a shared subunit between the two complexes. Using molecular biology and biochemical tools, we are now characterizing other components of the budding yeast CSN.
We are also curious to determine whether the CSN in budding yeast is comparable to other organisms despite its divergence. This will give us an indication of whether budding yeast is a reliable model system for CSN studies.
Figure 1: Schematic cartoon highlighting subunit arrangement and interactions between the canonical PCI complexes
Figure 2: The three PCI complexes: Subunits loss in S. cerevisiae
Table 1: CSN subunits Loss in unicellular organisms: Canonical composition of proteasome lid and CSN in Arabidopsis thaliana, compared to CSN subunits in various unicellular organisms (Aspergillus nidulans; Neurospora crassa; Schizosaccharomyces pombe; Cyanidioschyzon merolae; candida albicans, saccharomyces cerevisiae).
People in the lab
The ARF GAP-related family of zinc finger proteins. In English (+ Hebrew Synopsis), 109 pages. Accepted August 12 1999. Department of Biology, Technion – Israel Institute of Technology, Haifa, Israel. Supervisor: Prof. Dan Cassel.
20) Yu, Z., Kleifeld, O., Lande-Atir, A., Bsoul, M., Kleiman, M., Krutauz, D., Book, A., Vierstra, R,D., Hofmann, K., Reis, N., Glickman, M,H, and Pick, E. (2011). "Dual function of Rpn5 in twoPCI complexes, the 26S proteasome and COP9 signalosome". Molecular Biology of the Cell. Ref
19) Golan, A., Pick, E., Tsvetkov, L., Nadle,r Y., Kluger, H. and Stern, D,F. (2010). "Centrosomal Chk2 in DNA damage responses and cell cycle progession". Cell Cycle. 19: 9. Ref
18) Pick, E., Hofmann, K. and Glickman, M,H. (2009). "PCI complexes: Beyond the proteasome, CSN, and eIF3 Troika". Molecular Cell. 35: 260-264. Ref
17) Aziz, S,A., Davies, M., Pick, E., Zito, C., Jilaveanu, L., Camp, R,L., Rimm, D,L., Kluger, Y. and Kluger, H,M. (2009). "Phosphatidylinositol-3-kinase as a therapeutic target in melanoma". Clinical Cancer Research. 15: 3029-3036. Ref
16) Pick, E. and Pintard, L. (2009). "In the land of the rising sun with the COP9 signalosome and related Zomes. Symposium on the COP9 signalosome, Proteasome and eIF3". European Molecular Biology Organization Reports. 10: 343-348. Ref
15) Pick, E., McCarthy, M,M. and Kluger, H,M. (2008). "Assessing expression of apoptotic markers using large cohort tissue microarrays". Methods in Molecular Biology. 414: 83-93. Ref
14) McCarthy, M,M., Pick, E., Kluger, Y., Gould-Rothberg, B., Lazova, R., Camp, R,L., Rimm, D,L. and Kluger, H,M. (2007). "HSP90 as a marker of progression in melanoma". Annals of Oncology. 19 :590-594. Ref
13) Pick, E., Lau, O,S., Tsuge, T., Menon, S., Tong, Y., Dohmae, N., Plafker, S,M., Deng, X,W. and Wei, N. (2007). "Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes". Molecular and Cellular Biology. 27: 4708-4719. Ref
12) Pick, E., Kluger, Y., Giltnane, J,M, Moeder, C., Camp, R,L., Rimm, D,L. and Kluger, H,M. (2007). "High HSP90 expression is associated with decreased survival in breast cancer". Cancer Research. 67 :2932-2937. Ref
11) Burger, O., Pick, E., Zwickel, J., Klayman, M., Meiri, H., Slotky, R., Mandel, S., Rabinovitch, L., Paltieli, Y., Admon, A. and Gonen, R. (2004)."Placental protein 13 (PP-13): effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies". Placenta. 25: 608-622. Ref
10) Rinaldi, T., Pick, E., Gambadoro, A., Zilli, S., Maytal-Kivity, V., Frontali, L. and Glickman, M,H. (2004). "Participation of the proteasomal lid subunit Rpn11 in mitochondrial morphology and function is mapped to a distinct C-terminal domain". Biochemical Journal. 381: 275-285. Ref
9) Than, N,G., Pick, E., Bellyei, S., Szigeti, A., Burger, O., Berente, Z., Janaky, T., Boronkai, A., Kliman, H., Meiri, H., Bohn, H., Than, G,N. and Sumegi, B. (2004). "Functional analyses of placental protein 13/galectin-13". European Journal of Biochemistry. 271: 1065-1078. Ref
8) Maytal-Kivity, V., Pick, E., Piran, R., Hofmann, K. and Glickman, M,H. (2003). "The COP9 signalosome-like complex in S. cerevisiae and links to other PCI complexes". The International Journal of Biochemistry and Cell Biology. 35: 706-715. Ref
7) Maytal-Kivity, V., Piran, R., Pick, E., Hofmann, K. and Glickman, M,H. (2002)."COP9 signalosome components play a role in the mating pheromone response of S. cerevisiae". European Molecular Biology Organization Reports. 3: 1215-1221. Ref
6) Huber, I., Rotman, M., Pick, E., Makle,r V., Rothem, L., Cukierman, E. and Cassel, D. (2001)." Expression, purification, and properties of ADP-ribosylation factor (ARF) GTPase activating protein-1". Methods in Enzymology. 329: 307-316.
5) Szafer, E., Pick, E., Rotman, M., Zuck, S., Huber, I. and Cassel, D. (2000). "Role of coatomer and phospholipids in GTPase-activating protein-dependent hydrolysis of GTP by ADP-ribosylation factor-1".The Journal of Biological Chemistry. 275: 23615 23619.
4) Dogic, D., de-Chassey, B., Pick, E., Cassel, D., Lefkir, Y., Hennecke, S., Cosson, P. and Letourneur, F. (1999). "The ADP-ribosylation factor GTPase-activating protein Glo3p is involved in ER retrieval". European Journal of Cell Biology. 78: 305-310. Ref
3) Poon, P,P., Cassel, D., Spang, A., Rotman, M., Pick, E., Singer, R,A. and Johnston, G.C. (1999). "Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins with overlapping function". European Molecular Biology Organization Journal. 18: 555-564.
2) Gilad, E., Pick, E., Matzkin, H. and Zisapel, N. (1998). "Melatonin receptors in benign prostate
epithelial cells: evidence for the involvement of cholera and pertussis toxins-sensitive G proteins in their signal transduction pathways". Prostate. 35: 27-34.
1) Gilad, E., Laudon, M., Matzkin, H., Pick, E., Sofer, M., Braf, Z. and Zisapel, N. (1996). "Functional melatonin receptors in human prostate epithelial cells". Endocrinology. 137: 1412-1417.
Articles in Conference Proceedings
4) Kliman, H.J., Sammar, M., Lynch, S.K., Gimpel, Y., Pick, E., Bejar, J., Arad, A., Meiri, H. and Gonen, R. PP13 (Galectin 13) Mediated Zones of Necrosis Diverts the Maternal Immune Response Away from the Decidual Spiral Arterioles. (2008) International Society for the Study of Hypertension in Pregnancy
3) Aziz, S.A., Pick-Golan, E., McCarthy, M.M., Flaherty, K.T., Camp, R.L., Rimm, D.L., Kluger, H.M., Assessment of PI3 kinase as a druggable target in melanoma (2007) ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 25, No 18S Journal of Clinical Oncology, 8521 American Society of Clinical Oncology
2) Marei, S., Megan, S., Gebhardt, S., Pick-Golan, E., Meiri, H., Huppertz, B., Hillerman, R., RNA splicing and DNA polymorphism leading to two shorter sub-forms of PLACENTA PROTEIN 13 in preeclampsia (2006) American Journal of Obstetrics & Gynecology. 195 Supplement 6:S141 [AIF= 3.519 , C=5]
1) Boronkai, A., Bellye, S., Pick, E., Szigeti, A., Burger, O., Minik, O., Janaky, T., Kliman, H., Bohn, H., Meiri, H., Sumegi, B. and Than, N. Molecular biological characterization and functional analysis of PP13/galectin-13 (2005) FEBS Journal272 (s1) Abstract number: D2-007P [AIF=3.042]