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Review
. 2008 Aug;7(15):2333-40.
doi: 10.4161/cc.6368. Epub 2008 May 29.

Oncogene-induced senescence: an essential role for Runx

Anna Kilbey  1 , Anne Terry, Ewan R Cameron, James C Neil
Affiliations
Review

Oncogene-induced senescence: an essential role for Runx

Anna Kilbey et al. Cell Cycle. 2008 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Loss of Runx2 promotes Gadd54α transcription in response to activated Ras. cDNA was prepared from littermate matched Runx2-/- and WT cultures transduced with H-RasV12 or the PURO control vector and plated for 3 to 13 days in culture. Gadd45α expression was assayed at each timepoint by relative quantification to the day 3 WT sample and normalized to endogenous control hprt. The data is displayed as raw RQ values and is representative of two independent experiments on two littermate matched Runx2-/- and WT lines.
Figure 2
Figure 2
PI(3)K signaling is refractory to loss of Runx2 but uncoupled from p27Kip1 regulation. (A) Total protein was extracted from early passage (p4) littermate matched Runx2 null and WT lines following retroviral transduction with H-RasV12 (Ras) and plating in culture for up to 11 days. The blot was probed against antibodies to phospho-AKT (Cell Signalling #9271) or AKT1/2 (sc-8312) as a loading control and is representative of two independent experiments. (B) Total protein was extracted from early passage (p4) littermate matched Runx2 null and WT lines directly after retroviral transduction with H-RasV12 (R) or the PURO (P) vector control. The blot probed against an antibody to p27Kip1 (BD transduction labs. 610242). α Actin (sc-1616) was used as a loading control. (C) Western blot analysis as in (A) probed against antibodies to p27Kip1 and α Actin. (D) Immunoprecipitation (IP) of lysates extracted from H-RasV12 transduced Runx2 null and WT lines with an antibody to Cyclin D1 (Biosource DCS11). The blots were subsequently immunoblotted (IB) against antibodies to p27Kip1 and α cyclin D1. (E) Cell cultures as described in (D) were plated on poly-L-lysine coated chamber slides and labeled with an antibody to p27Kip1 and a second antibody coupled to FITC. DAPI containing mountant (Vector Labs) was used to visualize the nuclei.
Figure 3
Figure 3
Loss of Runx2 confers increased expression of SWI/SNF ATPases but does not prevent Ras-dependent repression of Brm. cDNA was prepared as for Figure 1.
Figure 4
Figure 4
Possible perturbation of the cellular senescence machinery by Runx transcription factors. 1. Runx1 elevates Rac1 activity (unpublished observations-A.K.). 2. Runx1 transcriptionally activates p19Arf expression. 3. Runx1 is cofactor for HIPK2 which facilitates acetylation of p53 on Lys382. 4. Runx and p53 binding sites feature in multiple p53 regulated genes. 5. Loss of Runx2 is associated with deregulated cyclin gene expression normally repressed by E2F:pRb:SWI/SNF complexes. 6. Runx proteins interact with chromatin remodeling factors recruited during senescence to mediate stable gene repression.
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