Protein kinase C-zeta reverts v-raf transformation of NIH-3T3 cells

被引:39
|
作者
Kieser, A
Seitz, T
Adler, HS
Coffer, P
Kremmer, E
Crespo, P
Gutkind, JS
Henderson, DW
Mushinski, JF
Kolch, W
Mischak, H
机构
[1] UNIV UTRECHT HOSP,DEPT PULM DIS,2584 CX UTRECHT,NETHERLANDS
[2] GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT GMBH,INST IMMUNOL,D-81377 MUNICH,GERMANY
[3] NIDR,MOLEC SIGNALING UNIT,NIH,BETHESDA,MD 20892
[4] NCI,MOLEC GENET SECT,GENET LAB,BETHESDA,MD 20892
关键词
protein kinase C-zeta; v-raf; suppression of transformation; junB induction; egr-1; induction; junB promoter;
D O I
10.1101/gad.10.12.1455
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have identified protein kinase C-zeta (PKC-zeta) as a novel suppressor of neoplastic transformation caused by the v-raf oncogene. PKC-zeta overexpression drastically retards proliferation, abolishes anchorage-independent growth, and reverts the morphological transformation of v-raf-transformed NIH-3T3 cells. The molecular basis for this effect appears to be a specific induction of junB and egr-1 expression, triggered synergistically by PKC-zeta via a Raf/Mek/MAPK-independent mechanism and v-raf. junB-promoter/CAT assays revealed that PKC-zeta directly targets the junB promoter. The induction of junB and egr-1 is linked to the v-raf transformation-suppressing effect of PKC-zeta as constitutive expression of junB and egr-1 but not of c-jun also abolishes anchorage-independent growth of v-raf-transformed NIH-3T3 cells. Moreover, junB overexpression leads to a retardation of proliferation in these cells. PKC-zeta interferes with the serum inducibility of an AP-1 reporter plasmid in v-raf-transformed NIH-3T3 cells, indicating that PKC-zeta antagonizes transformation and proliferation by down-modulating AP-1 function via induction of junB. In summary, our data suggest that PKC-zeta counteracts v-raf transformation by modulating the expression of the transcription factors junB and egr-1.
引用
收藏
页码:1455 / 1466
页数:12
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