Overexpression of Mos^rat proto‐oncogene product enhances the positive autoregulatory loop of MyoD

Abstract

The myogenic b-HLH transcription factor MyoD activates expression of muscle-specific genes and autoregulates positively its own expression. Various factors such as growth factors and oncogene products repress transcriptional activity of MyoD. The c-mos proto-oncogene product, Mos, is a serine/ threonine kinase that can activate myogenic differentiation by specific phosphorylation of MyoD which favors heterodimerization of MyoD and E12 proteins. Here we show that overexpression of Mos enhances the expression level of MyoD protein in myoblasts although phosphorylation of MyoD by Mos does not modify its stability but promotes transcriptional transactivation of the MyoD promoter linked to the luciferase reporter gene. Moreover, co-expression of MyoD with Mos wt but not with the kinase-inactive Mos KM greatly enhances expression of endogenous MyoD protein and the DNA binding activity of MyoD/E12 heterodimers in 10T1/2 cells. Our data suggest that Mos increases the ability of MyoD to transactivate both musclespecific genes and its own promoter and could therefore participate in the positive autoregulation loop of MyoD and muscle differentiation.z 1998 Federation of European Biochemical Societies.

Critical Role for Lysine 133 in the Nuclear Ubiquitin-mediated Degradation of MyoD

“…When analyzed by pulse-chase experiments and/or cycloheximide treatment (Fig. 1C), the half-life of MyoD-wt was ϳ50 min (24,25) and that of HA-MyoD was roughly identical (45 and 50 min, respectively), indicating that the replacement of the NH 2 -terminal Met residue by the 3ϫ HA tag does not noticeably affect the stability of MyoD in vivo. These data suggest that the NH 2 terminus-dependent pathway and the lysine-dependent pathway have the same activity in the nuclear degradation of MyoD.…”

Hypoxia Inhibits Myogenic Differentiation through Accelerated MyoD Degradation

“…Hypoxia Accelerates MyoD Protein Degradation-Previous reports establish the MyoD half-life at about 40 min (33,35,36) and establish that phosphorylation is required for its cell cycleregulated degradation (36). To analyze whether hypoxia affected MyoD protein stability by increasing its turnover, MyoD accumulation was determined in C2C12 cells after cyclohexi- FIG.…”

c‐mos immunoreactivity is an indicator of good prognosis in lung cancer

“…Moreover, the appropriate formation and orientation of the meiotic spindle that leads to asymmetric division of the oocyte and production of the first polar body is associated with c‐mos activity 10 . On the other hand, in somatic cell lines, there are data showing that c‐mos is implicated in mitogenic signalling during G1 phase leading to cellular transformation, 8 , 11 cell arrest, 12 apoptosis 12 , 13 and cell differentiation 14 . These functions seem to be dependent on the expression levels of c‐mos and the status of its downstream effectors 8 ,.…”