TRIM22/Staf50 - a novel target gene of the tumor suppressor p53

Sammanfattning: The tumor suppressor gene p53 is a transcription factor that mediates cell cycle arrest, apoptosis and differentiation. p53 mediated differentiation of leukemic cells depends on the transcriptional activity of p53 but so far no obvious differentiation inducing target gene has been identified. Using a cDNA microarray analysis, I identified TRIM22/Staf50 as a novel direct target gene to p53. The function of TRIM22 is largely unknown apart from being an interferon inducible protein and its involvement in inhibiting virus infection. TRIM22 belongs to the family of TRIM proteins (RBCC proteins) consisting of a RING finger, a B-box, a coiled-coil and a variable C-terminal. The TRIM proteins have been shown to be involved in cellular processes like virus infection, ubiquitination, differentiation and apoptosis.

I have found that overexpression of TRIM22 increases cell death and co-localizes with the tumor suppressor PML. Interestingly, PML is also interferon inducible, a member of the TRIM family (TRIM19) and involved in functions like apoptosis and viral defense. Furthermore I found that TRIM22 have a role in hematopoietic differentiation and in T lymphocyte activation.

Given that TRIM22 mediates cell death and has a role in differentiation and viral defense, I suggest that TRIM22 could be the link between p53 tumor suppression pathways and interferon response pathways. However, further experiments are necessary to reveal the mechanisms of TRIM22 in order to connect these two pathways.