Activating transcription factor 4 (ATF4), a member of the cyclic adenosine monophosphate responsive element-binding (CREB) protein family, was found to be a direct target of CLOCK, and downregulation of either CLOCK or ATF4 increased susceptibility of A549 lung cancer cells to cisplatin and etoposide, which suggests that CLOCK and ATF4 transcription system plays an important role in chemosensitivity [44]. The gene discussed is CLOCK; the disease is lung cancer.