Cell proliferation inhibited by MyoD1 independently of myogenic differentiation
Open Access
- 1 June 1990
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 345 (6278), 813-815
- https://doi.org/10.1038/345813a0
Abstract
CELL growth and differentiation are usually mutually exclusive1. Transformation of myoblasts by retroviruses containing the myc oncogene inhibits differentiation, preventing cells from withdrawing from the cell cycle4,5. If cell-cycle withdrawal is a prerequisite for myoblast differentiation, it is probably an early event in terminal cell differentiation, but this has not yet been established6. MyoD1 regulates myogenesis7. It is expressed only in skeletal muscle8, but can convert other cells to muscle cells9,10. The MyoD1 protein, a nuclear phosphoprotein in part similar to the myc family of proteins, is a DNA-binding protein binding to the enhancer sequences of the muscle-specific creatine phosphokinase gene11. Thus, introduction of MyoD1 into cells provides a simple approach to study the effect of induction of differentiation on cell growth. In cultured NIH 3T3 cells, inhibition of cell proliferation occurs within 18 hours, and expression of myosin starts after 72 hours. Furthermore, injection of MyoD1 into quiescent NIH3T3 cells inhibits the serum-induced G0–S phase transition of the cell cycle. In CV1 cells, which are not induced to differentiate by MyoD1, DNA synthesis is also inhibited. Expression of MyoD1 can thus inhibit cell proliferation independently of induction of differentiation. Deletion of the myc-like domain in the MyoD1 gene12 eliminates the inhibition of DNA synthesis, but substitution of the basic domain with the analogous domain from the E12 transcription factor13 inhibits growth yet fails to induce differentiation. Inhibition of DNA synthesis, therefore, seems to be controlled separately from myogenic differentiation.Keywords
This publication has 16 references indexed in Scilit:
- The MyoD DNA binding domain contains a recognition code for muscle-specific gene activationCell, 1990
- Expression of two myogenic regulatory factors myogenin and MyoDl during mouse embryogenesisNature, 1989
- MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancerCell, 1989
- Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequenceCell, 1989
- Interaction with normal cells suppresses the transformed phenotype of v-myc-transformed quail muscle cellsCell, 1989
- Single cell assay with an automated capillary microinjection systemExperimental Cell Research, 1988
- Expression of a single transfected cDNA converts fibroblasts to myoblastsCell, 1987
- The expression of three members of the achaete-scute gene complex correlates with neuroblast segregation in DrosophilaCell, 1987
- Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro.The Journal of cell biology, 1982
- Lineages, quantal cell cycles, and the generation of cell diversityQuarterly Reviews of Biophysics, 1975