TY - JOUR
T1 - Translational control of protein kinase Cη by two upstream open reading frames
AU - Raveh-Amit, Hadas
AU - Maissel, Adva
AU - Poller, Jonathan
AU - Marom, Liraz
AU - Elroy-Stein, Orna
AU - Shapira, Michal
AU - Livneh, Etta
PY - 2009/11
Y1 - 2009/11
N2 - 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, PKCη, 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 PKCη 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 PKCη in MCF-7 growing cells. While the two uORFs function as repressive elements that maintain low basal levels of PKCη 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-2α 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.
AB - 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, PKCη, 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 PKCη 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 PKCη in MCF-7 growing cells. While the two uORFs function as repressive elements that maintain low basal levels of PKCη 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-2α 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.
UR - http://www.scopus.com/inward/record.url?scp=71949111384&partnerID=8YFLogxK
U2 - 10.1128/MCB.01044-09
DO - 10.1128/MCB.01044-09
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AN - SCOPUS:71949111384
SN - 0270-7306
VL - 29
SP - 6140
EP - 6148
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 22
ER -