Gender	Male
E-mail	zeev.ronai@mssm.edu
	daphne.pabst@mssm.edu
Education and Training	, Columbia University
	Ph.D., The Hebrew University
Awards	Research Grants multiple NIH sponsored research grants to study mechanisms underlying the resistance of tumors to treatment with focus on ATF2, p53, Mdm2 and their kinases. NIH/NCI
	2000 Karolinska Nobel Conference on Ubiquitin
	1997 Hiroshima Cancer Seminar
	1982 Golda Meir Fellow

Education and Training	, Columbia University
	Ph.D., The Hebrew University

JNK targeted ubiquitination of its associated proteins - the search for JNK-dependent ligase

Former studies in our lab have established the role of JNK in targeting the ubiquitination of degradation of its associated transcription factors substrates. This important phenomena was demonstrated for c-Jun, ATF2 and p53, and occurs under normal growth conditions, when JNK is not active as a kinase. In all cases, activation of JNK by stress, followed by its phosphorylation of associated substrates results in their stabilization. We therefore seek to identify the mechanism underlying JNK ability to target its associated proteins for ubiquitination and degradation. We hypothesize that such protein may be part of E3 ligase complex, or alternatively be a RING finger protein with potent E3 ligase. Recent studies via mass spec analysis of JNK bound proteins enabled the identification of novel partners which could mediate changes in stability of JNK-associated substrates, aspects which are currently under invesitgation.

Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z. JNK targets p53 ubiquitination and degradation in nonstressed cells. Genes Dev 1998 Sep 1; 12(17): 2658-63.

Fuchs SY, Ronai Z. Ubiquitination and degradation of ATF2 are dimerization dependent. J Biol Chem 1999; 19: 3289-3298.

Fuchs SY, Chen A, Xiong Y, Ronai Z. HOS, a human homologue of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkB and b-catenin. Oncogene 1999 Mar 25; 18(12): 2039-46.

Adler V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ, Ronai Z. Regulation of JNK signaling by GSTp. EMBO J 1999 Mar; 18(5): 1321-34.

Buschmann T, Adler V, Matusevich E, Fuchs SY, Ronai Z. p53 phosphorylation and association with murine double minute 2, c-Jun NH2-terminal kinase, p14ARF, and p300/CBP during the cell cycle and after expos. Cancer Res 2000 Feb 15; 60(4): 896-900.

Ivanov VN, Bhoumik A, Krasilnikov M, Raz R, Owen-Schaub LB, Levy D, Ronai Z. Cooperation between STAT3 and c-Jun suppresses Fas transcription. Mol Cell 2001; 7: 517-528.

Cho S, Bhoumik A, Broday L, Ivanov V, Rosenstein B, Warburton P, Ronai Z. TIP49bD a regulator of activating transcription factor 2 (ATF2) response to stress and DNA damage. Mol Cell Biol 2001 December; 21(24): 8398-8413.

Bhoumik A, Ivanov V, Ronai Z. ATF2-derived peptides alter resistance of human tumor cell lines to UV-irradiation and chemical treatment. Clin Cancer Res 2001; 7: 331-342.

Buschmann T, Fuchs SY, Fried VA, Ivanov VN, Alacron-Vargas D, Pincus M, Ronai Z. Jun NH2-Terminal Kinase Phosphorylation of p 53 on Thr-81 Is Important for p53 Stabilization and Transcriptional Activities in Response to Stress. Mol Cel Biol 2001; 21: 2743-2754.

Ivanov I, Bhoumik A, Krasilnikov M, Raz R, Owen-Sachaub LB, Levy D, Ronai Z. Cooperation between STAT3 and c-Jun suppresses Fas transcription. Mol Cell 2001; 7: 517-528.

Habelhah H, Shah K, Huang L, Ostareck-Lederer A, Burlingame AL, Shokat KM, Hentze MW, Ronai Z. ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and subsequent inhibition of mRNA translation. Nat Cell Biol 2001; 3: 3:325-330.

Habelhah H, Hunag L, Burlingame AL, Shokat MW, Ronai Z. Identification of New JNK Substrate Using ATP Pocket Mutant JNK and a Corresponding ATP Analogue. J Biol Chem 2001; 276: 18090-18095.

Ivanov VN, Fodstad , Ronai Z. Expression of RING finger-deleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFa and suppression of NF-kB activities. Oncogene 2001; 20: 2243-2253.

Ronai Z. An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis.. J. Clinical Invest. 2002;.

Ronai Z. FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface.. Mol Cell Biol 2003;.

Ronai Z. RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization . Mol Cell Biol 2003;.

Ronai Z. Mdm2: A regulator of cell growth and death.. Adv Cancer Res 2003; 89: 1-34.

Ronai Z. Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB.. EMBO J 2004 January;.

Ronai Z. ATF2-derived peptide induces transcriptional switch which sensitizes melanoma to apoptosis and inhibit their tumorigenicity. Proc. Natl. Acd. Sci USA 2004 March;.