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. 2011 Mar 11;30(8):1536–1548. doi: 10.1038/emboj.2011.69

Figure 3.

Figure 3

Constitutive p38MAPK activation is sufficient to induce an SASP. (A) PRE cells were infected with lentivirus expressing a constitutively active MAP kinase kinase 6 mutant (MKK6EE). Whole cell lysates were collected 8 days after infection and analysed by western blot. Presenescent controls (PRE) were infected with insertless vector. (B) MKK6EE induces p38MAPK-dependent growth arrest. Cells were infected as in (A) and counted at the indicated intervals thereafter. +SB: p38MAPK was continuously inhibited by SB203580 beginning 48 h before infection. (C) MKK6EE induces an SASP. Cells were infected as described in (A); CM were collected 8 days after infection. +SB: p38MAPK was inhibited by SB203580 for 48 h before CM collection. Secreted proteins were analysed using antibody arrays. Shown are proteins for which the MKK6EE level was significantly increased (P<0.05) over PRE. PRE and MKK6EE values were averaged to generate the baseline. Heat map and dendrogram were generated as in Figure 1E. *: Factors significantly decreased by p38MAPK inhibition (P<0.05). (D) The MKK6EE SASP resembles SEN(XRA) and SEN(RAS) SASPs. Shown are the 10 most upregulated factors in the SEN(XRA) and SEN(RAS) SASPs. +: Factors significantly increased by MKK6EE expression.