TRIMming p53 for ubiquitination

The function of the p53 tumor suppressor protein is finely tuned through a myriad of interactions with other proteins. These interactions can lead to posttranslational modifications that regulate p53 stability, DNA binding, or promoter-specific transcriptional activation. A number of p53 binding proteins serve as cofactors that participate in the recruitment of p53 to specific promoters and facilitate transcriptional activation by p53. Other p53-interacting proteins regulate transcription-independent activities of p53 and p53 subcellular localization (reviewed in refs. 1 and 2). A new p53 binding partner is identified by Allton et al. (3) in this issue of PNAS, and it turns out to be a member of the tripartite motif protein (TRIM) family, TRIM24. The TRIM family of proteins is defined by the presence of an N-terminal tripartite motif composed of a RING domain, 1 or 2 B-box motifs, and a coiled-coil region (4). Humans have 60 TRIM genes, and these encode proteins that can be further classified on the basis of 1 or 2 additional C-terminal domains. One subgroup, consisting of TRIM24, TRIM28, and TRIM33 [also known as transcription intermediary factor 1 (TIF1) α, TIF1β, and TIF1γ, respectively], contains a PHD domain followed by a BROMO domain at the C terminus. These domains are important for binding to chromatin and are involved in transcriptional repression. TRIM24 protein interacts with retinoic …