Abstract 2967: The p53 target gene TRIM22 colocalizes with the centrosome independently of cell cycle phase

Abstract

Abstract TRIM22 (Staf50) is an interferon (IFN)-inducible protein as well as a p53 target gene. The specific molecular function of TRIM22 is largely unknown, but TRIM22 is suggested to play a role in viral defense by restriction of viral replication. Furthermore, TRIM22 may function as an ubiquitin E3 ligase, targeting proteins for degradation. TRIM22 is highly expressed in lymphoid tissues as well as in peripheral blood leukocytes and in the ovary and lung. TRIM22 belongs to the TRIM family of proteins, named based on a characteristic tripartite-motif (TRIM), including a RING-finger, one or two B-boxes and a coiled-coil domain. The TRIM family consists of more than 70 proteins, implicated in diverse biological processes such as apoptosis, cell proliferation, viral defense and ubiquitylation. Several TRIM family members are involved in cancer. Interestingly, TRIM proteins have been suggested to identify specific cell compartments by means of multimerization. There have previously been conflicting reports regarding the subcellular localization of exogenous TRIM22. Utilizing immunoflourescence and subcellular fractionation, we show here that endogenous TRIM22 is localized to both nucleus and cytosol in the human osteosarcoma cell line U2OS. Furthermore, the same localization pattern is present in human peripheral blood mononuclear cells (PBMCs), an environment more relevant to its physiological function. Moreover, we demonstrate a colocalization of TRIM22 with the centrosomes in U2OS cells as well as in PBMCs, and show that this colocalization is independent of cell cycle phase, utilizing the centrosome markers gamma-tubulin, aurora A and pericentrin. The centrosomal localization was confirmed with electronic microscopy, suggesting TRIM22 to be localized in the pericentriolar material (PCM) and not at any specific site at the centrioles. Additionally, the colocalization with centrosomes appears to be independent on the microtubule network as shown by the microtubuli destabilizing agent nocodazole. Centrosomes are essential organelles, vital for mitosis and organization of the microtubule network as well as providing sites for viral replication, viral assembly and protein degradation. Our data suggest that centrosomal TRIM22 may have important functions in these processes. However, further studies are required to confirm this notion. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2967.