Functional Characterization of a Ring-Finger Protein, Greull

摘要

RING-finger containing proteins such as MDM2, WT1 and BRCA1 have been shown to modulate the function of tumor suppressor p53. Like MDM2, a RING-finger protein, Greull (Goliath Related E3 Ubiquitin Ligase 1) is recently identified to function as an E3 ubiquitin ligase. In this work, we explore the potential role of Greull in regulating the cellular function of p53, and we found that Greull can specifically prevent cells from apoptosis induced by p53. The RING-finger motif has been identified in a large and diverse family of regulatory proteins that includes transcriptional factors, proto-oncogenes, tumor suppressors and proteins that affect DNA recombination or repair (Borden and Freemont, 1996). This motif binds zinc/ divalent metal ions to form a structure that may also be involved in protein-protein interaction (Freemont et al., 1991). To date, three RING-finger containing proteins, MDM2 (Boddy et al., 1994), WT1 (Maheswaran et al., 1995) and BRCA1 (Chen et al., 1998), have been shown to interact with p53 and modify its function in several different aspects. One E3 ubiquitin ligase family, which has been found to catalyze polyubiquitination, is the C3H2C3 RING fingers (Joazeiro and Weissman, 2000), and Mdm2 was shown to associate with and ubiquitinate p53 (Fang et al., 2000). Recently, centre dot Greull is identified as an E3 ubiquitin ligase and plays a role in the induction of anterior ectoderm during Xenopus development (Borchers et al., 2002). Here we evaluate whether the RING-finger containing Greull will affect the cellular function of p53 in cultured cells.