The interferons (IFNs) have antimicrobial, antitumor, cell growth regulatory and immunomodulatory activities and they also affect differentiation. Their various activities are performed by proteins that are encoded by IFN-activatable genes. Earlier we have described a cluster (gene 200 cluster) Of at least six, structurally related, IFN- activatable genes (Ifi201, Ifi202a* and b, Ifi203, Ifi204 and D3). These arose in consequence of repeated gene duplications. They encode the 200 family of proteins (p202a and b, p203, p204 and D3). Overexpression of p202a, p202b or p204 results in an inhibition of cell proliferation. In the case of p202a this might be correlated with the inhibition of the activity of several transcription factors, including c-Fos, c-Jun, AP2, E2F1, E2F4, MyoD, myogenin, NF-kB p50 and 65, p53 and c-Myc. In most of these cases, p202a binds the factor and inhibits its sequence-specific binding to DNA. p202a also binds the p53 Binding Protein l, this results in the inhibition of p202a activity. p204, which in fibroblasts is primarily nucleolar, inhibits ribosomal RNA synthesis by binding the UBF1 transcription factor and inhibiting its sequence-specific binding to DNA. The level of p202a strongly increases during skeletal muscle differentiation. In myoblasts p202a inhibits the expression of MyoD, as well as the activities of MyoD and myogenin. p202a is strongly antiapoptotic. We have knocked out the Ifi202a gene from mice, however, this resulted in the compensatory overexpression of the highly similar Ifi202b gene, and gave rise to no new phenotype. We have been collaborating with a sequencing laboratory in the sequencing and the characterization of the murine and human gene 200 clusters. The sequence is required for the knockout of a group of genes in the gene 200 cluster from mice and from murine cardiac ventricular muscle using the Cre/lox procedure. We plan to examine the effects of these knockouts and also to proceed with the study of the biological and biochemical functions of p202a and b, and p204 in muscle differentiation and IFN action using a large variety of approaches. *Ifi202a was designated earlier as Ifi202. Ifi202b, recently identified, encodes p202b, a protein that differs from p202a only in 7 of 445 amino acids.
| Lengyel, Peter; Liu, C J (2010) The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey. Cell Mol Life Sci 67:335-40 |
| Liu, Chuan-ju; Ding, Bo; Wang, Hong et al. (2002) The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins. Mol Cell Biol 22:2893-905 |
