The activating transcription factor-4 (ATF-4) is involved in the cellular stress response. In a recent report we demonstrated that the protein stability of ATF-4 is regulated oxygen-dependently by the prolyl-4-hydroxylase-domain (PHD) 3 oxygen sensor, indicating that cellular oxygen availability is linked to cell fate decisions. Here we characterize the oxygen-mediated ATF-4 degradation pathway in normoxia. Normoxic ATF-4 destabilization is due to ubiquitination as demonstrated by ATF-4 immunoprecipiation and anti-ubiquitin immunoblots. ATF-4 ubiquitination is oxygen-dependently regulated since hypoxia inhibited this process. The ubiquitin E3 ligase ß-TRCP was reported to regulate ATF-4 stability previously. Its function in normoxic degradation of ATF-4, however, is not known to date. Here we excluded an involvement of ß-TRCP in normoxic destabilization of ATF-4 by siRNA treatment targeting ß-TRCP. Taken together our data indicate a putative involvement of oxygen-dependent ATF-4 ubiquitination in cell fate decision.