Both ERK1 and ERK2 kinases promote G2/M arrest in etoposide-treated MCF7 cells by facilitating ATM activation

摘要: The MEK-ERK pathway plays a role in DNA damage response (DDR). This has been thoroughly studied by modulating MEK activation. However, much less done to directly examine the contributions of ERK1 and ERK2 kinases DDR. Etoposide induces G2/M arrest variety cell lines, including MCF7 cells. damage-induced depends on activation protein kinase ataxia-telangiectasia mutated (ATM). ATM subsequently activates CHK2 phosphorylating threonine 68 (T68) inactivates CDC25C via phosphorylation its serine 216 (S216), resulting arrest. To determine contribution etoposide-induced arrest, we individually knocked-down cells using specific small interfering RNA (siRNA). Knockdown either significantly reduced etoposide treatment, thereby attenuated substrates, S139 H2AX (gammaH2AX), p53 S15, T68. Consistent with these observations, knockdown or S216 compromised Taken together, demonstrated that both play facilitating pathway. These observations suggest cellular threshold level ERK activity is required for proper checkpoint