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Molecular and Cellular Biology, November 2009, p. 6140-6148, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.01044-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Translational Control of Protein Kinase C{eta} by Two Upstream Open Reading Frames {triangledown}

Hadas Raveh-Amit,1 Adva Maissel,1 Jonathan Poller,1 Liraz Marom,3 Orna Elroy-Stein,3 Michal Shapira,2 and Etta Livneh1*

Department of Microbiology and Immunology,1 Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel,2 Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel3

Received 6 August 2009/ Accepted 8 September 2009

Protein kinase C (PKC) represents a family of serine/threonine kinases that play a central role in the regulation of cell growth, differentiation, and transformation. Posttranslational control of the PKC isoforms and their activation have been extensively studied; however, not much is known about their translational regulation. Here we report that the expression of one of the PKC isoforms, PKC{eta}, is regulated at the translational level both under normal growth conditions and during stress imposed by amino acid starvation, the latter causing a marked increase in its protein levels. The 5' untranslated region (5' UTR) of PKC{eta} 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{eta} in MCF-7 growing cells. While the two uORFs function as repressive elements that maintain low basal levels of PKC{eta} in growing cells, they are required for its enhanced expression upon amino acid starvation. We show that the translational regulation during stress involves leaky scanning and is dependent on eIF-2{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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Phone: 972-8-647-7294. Fax: 972-8-647-7626. E-mail: etta{at}bgu.ac.il

{triangledown} Published ahead of print on 21 September 2009.

Molecular and Cellular Biology, November 2009, p. 6140-6148, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.01044-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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