Ze'ev A Ronai, PhD
- ADJUNCT PROFESSOR | Oncological Sciences
PhD, The Hebrew University
Karolinska Nobel Conference on Ubiquitin
Hiroshima Cancer Seminar
Golda Meir Fellow
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, 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.
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.
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.
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.
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.
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. Mdm2: A regulator of cell growth and death.. Adv Cancer Res 2003; 89: 1-34.
Ronai Z. ATF2-derived peptide induces transcriptional switch which sensitizes melanoma to apoptosis and inhibit their tumorigenicity. Proc. Natl. Acd. Sci USA 2004 March;.