MyoD-Dependent Induction during Myoblast Differentiation of p204, a Protein Also Inducible by Interferon

Abstract

p204, an interferon-inducible p200 family protein, inhibits rRNA synthesis in fibroblasts by blocking the binding of the upstream binding factor transcription factor to DNA. Here we report that among 10 adult mouse tissues tested, the level of p204 was highest in heart and skeletal muscles. In cultured C2C12 skeletal muscle myoblasts, p204 was nucleoplasmic and its level was low. During myoblast fusion this level strongly increased, p204 became phosphorylated, and the bulk of p204 appeared in the cytoplasm of the myotubes. Leptomycin B, an inhibitor of nuclear export that blocked myoblast fusion, inhibited the nuclear export signal-dependent translocation of p204 to the cytoplasm. The increase in the p204 level during myoblast fusion was a consequence of MyoD transcription factor binding to several MyoD-specific sequences in the gene encoding p204, followed by transcription. Overexpression of p204 (in C2C12 myoblasts carrying an inducible p204 expression plasmid) accelerated the fusion of myoblasts to myotubes in differentiation medium and induced the fusion even in growth medium. The level of p204 in mouse heart muscle strongly increased during differentiation; it was barely detectable in 10.5-day-old embryos, reached the peak level in 16.5-day-old embryos, and remained high thereafter. p204 is the second p200 family protein (after p202a) found to be involved in muscle differentiation.

Comparative transcriptome analysis of muscular dystrophy models Largemyd, Dmdmdx/Largemyd and Dmdmdx: what makes them different?

“…This gene, Ifi204, produces a protein at higher levels during myoblasts fusion, under the action of MyoD. Ifi204 overexpression accelerates myoblasts fusion, 44 as it reduces Id proteins levels, known for inhibit muscle differentiation by blocking MyoD and other myogenic proteins. 45 On the basis of this information, we hypothesize that Ifi204 downregulation in Dmd mdx / Large myd − / − could hamper myogenesis, unlike Dmd mdx that upregulates Ifi204 and shows a better regenerative potential.…”

p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

“…Overexpression of p204 was found to delay the progression of cells from the G0/G1 phase to the S phase of the cell cycle (Lembo et al, 1998). p204 was found to be an important regulator of both skeletal and cardiac muscle differentiation (Liu et al, 2000(Liu et al, , 2002Ding et al, 2006a,b). Overexpression of p204 accelerates muscle formation (Liu et al, 2000).…”

“…p204 was found to be an important regulator of both skeletal and cardiac muscle differentiation (Liu et al, 2000(Liu et al, , 2002 Ding et al, 2006a,b). Overexpression of p204 accelerates muscle formation (Liu et al, 2000). This is due at least in part to the binding of p204 to the Id proteins, including Id1, Id2, and Id3, and overcoming the inhibition by the Id proteins of MyoD activity in skeletal muscle differentiation, and Gata4 and Nkx2.5 activity in cardiac myocyte formation (Liu et al, 2002;Ding et al, 2006b).…”

“…p204 consists of 640 amino acid (aa) residues. In the N-terminal domain (aa 1-216), there is a basic amino acid-rich nuclear localization signal (NLS) and a canonical export signal (NES) required for the translocation of p204 from the nucleus to the cytoplasm during skeletal and cardiac muscle differentiation (Liu et al, 2000;Ding et al, 2006b). The C-terminal domain of p204 consists of two homologous, partially conserved 200-amino acid segments (a and b) in which pRb binding motifs (e.g., LXCXE) are located.…”

The Interferon-inducible p202a Protein Modulates NF-κB Activity by Inhibiting the Binding to DNA of p50/p65 Heterodimers and p65 Homodimers While Enhancing the Binding of p50 Homodimers

“…Overexpression of p204 in transfected mammalian cells leads to inhibition of growth (6,7). p204 is required for the differentiation of cultured myoblasts to myotubes, and the level of p204 increases during differentiation as a consequence of transactivation of the gene by MyoD (8). p204 enables the differentiation in part by overcoming the inhibition of the activities of MyoD, E12/E47, and other myogenic transcription factors by the Id proteins, Id1, Id2, and Id3 (9) (see also Ref.…”