FIGURE 4.

Constitutively active p38α and p38γ, but not p38β, induce premature senescence in primary human fibroblast cells. A and B, Western blot analysis of BJ cells transduced with vector control (Babe Puro, BP). Ha-RasV12 (Ras), hemagglutinin-tagged wild type p38α, p38γ, or p38β (WT), or their active mutants (p38αD176A, p38γD179A, or p38βD176A) was performed to detect the indicated proteins. Cells were lysed on day 8 post-transduction at PD33. C, the population doublings of the BJ cell lines described in A and B were followed for 6 (left panel) or 12(middle and right panels) days, starting on day 5 post-transduction at PD32. Values are mean ± S.D. for duplicates. ^*, p < 0.001; ^**, p < 0.01; #, p > 0.05, versus vector control by Student's t test. D, BJ cell lines (described in A) were stained for the SA-β-gal senescence marker on day 14 post-transduction. Values in are mean ± S.D. for duplicates. ^*, p < 0.01; #, p > 0.05, versus vector control by Student's t test.