We identify the transcription factor ATF4 to be a key mediator of tumor suppression by the PKR/eIF2α-P arm via the upregulation of the cyclin dependent kinase (CDK) inhibitor P21Cip1 and activation of the c-Jun-N-terminal kinase 1/2 (JNK1/2). The gene discussed is MAP2K4; the disease is neoplasm.