Prof. Etta Livneh

Prof. Etta Livneh Profile

Professor Emeritus
Ph.D., 1981

Department : Shraga Segal Department of Microbiology, Immunology and Genetics
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cancer,alzheimer, molecular biology, inflammation


  • 1981-Ph.D (Photochemistry) Weizmann Inst. of Science; 1982-1984, Stanford University, CA Post-Doc, Molecular Biology.

Research Interests

  • Tumor biology;
  • Molecular Mechanisms of Breast Cancer;
  • Signal Transduction of proliferation and differentiation;
  • Protein kinase C;
  • Cell cycle regulation;
  • PKC in drug resistance and apoptosis;
  • Regulation of phosphorylation;
  • Nucleocytoplasmic shuttling;
  • Translational regulation;

Research Projects

  • Role of PKC in the resistance to chemotherapy and cell death 2) Translational regulation of PKC via upstream open reading framed (uORFs) 3) Cancer stem cells (CRC) in breast cancer 4) PKC as a prognostic and therapeutic target in breast cancer 5) Signaling pathways and cell cycle regulation in breast cancer

Research Abstract

  • PKC h confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells Noa Rotem-Dai, Galia Oberkovitz*, Sara Abu-Ghanem and Etta Livneh. Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKC h , confers protection against apoptosis induced by the DNA damaging agents, UVC-irradiation and the anti-cancer drug- Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKC h in MCF-7 cells, under the control of the tetracycline- responsive promoter, resulted in increased cells survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKC h . Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKC h expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKC h is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKC h could represent a target for intervention aimed to reduce resistance to anti-cancer treatments. 2) Translational Control of Protein Kinase C h by Two Upstream Open Reading Frames (uORFs) Hadas Raveh-Amit 1 , Adva Maissel 1 , Jonathan Poller 1 , Liraz Marom 3 , Orna Elroy-Stein 3 , Michal Shapira 2 and Etta Livneh 1* Protein kinase C (PKC) represents a family of serin/threonine kinases, playing a central role in the regulation of cell growth, differentiation and transformation. Post-translational control of the PKC isoforms and their activation has been extensively studied, however, not much is known on their translational regulation. Here we report that the expression of one of the PKC isoforms, PKC h , is regulated at the translational level both under normal growth conditions and during stress imposed by amino acids starvation, the latter causing a marked increase in its protein levels. The 5'-untranslated region (5'UTR) of PKC h is unusually long and GC rich, characteristic of many oncogenes and growth regulatory genes. We have identified two conserved upstream open reading frames (uORFs) in its 5'UTR and show their effect in suppressing the expression of PKC h in MCF-7 growing cells. While the two uORFs function as repressive elements that maintain low basal levels of PKC h in growing cells, they are required for its enhanced expression upon amino acids starvation. We show that the translational regulation during stress involves leaky scanning and is dependent on eIF2-alpha phosphorylation by GCN2 . Our work further suggests that translational regulation could provide an additional level for controlling the expression of PKC family members, being more common than currently recognized.

Research Topics

  • The resistance cancer cells to stress and chemotherapy- role of PKC
  • PKC as a prognostic factor in breast and lung cancer patients
  • Novel translational regulation of PKC via upstream open reading frames ( uORFs )
  • Increased risk for cerebral infarction and rheumatoid arthritis - polymorphic changes in PKCeta
  • Role of PKC in Alzheimer disease

Major expertise and techniques in the lab

  • Signal transduction
  • Immunfluorescence and immunohistochemistry
  • Molecular biology and exogenous expression of proteins

Publications and funding summary / representative publications and grants

  • Tamarkin *, A., Zurgil *, U., Hai , N., Krasnitsky , E., Maissel , A., Yankelovich , L. Livneh , E. DNA damage targets PKC h to the nuclear membrane via its C1B domain. Experimental Cell Research. 311: 1465-1475 (2011). Shahaf , G., Koifman , G., Rotem-Dai, N., Raveh-Amit , H. and Livneh , E. PKC h is a negative regulator of AKT inhibiting the IGF-1 induced proliferation. Experimental Cell Research. 318: 789-799 (2012). Krasnitsky , E., Baumfeld , Y., Freedman, J., Sion -Vardy, N., Ariad , S., Novack , V. and Livneh , E. PKC? Is a Novel Prognostic Marker in Non-small Cell Lung Cancer. Anticancer Res. 32: 207-215 (2012).
  • The Israel Science Foundation (ISF)

Existing collaborations

  • Alon Monsonego - PKC in Alzheimer disease
  • Roni Apte - PKC and inflammation
  • Michal Shapira (BGU) and Orna Elroy-Stein (TAU)- PKC and translational control