Regulation of cell differentiation in C2C12 myoblasts by the Id3 helix-loop-helix protein.
To investigate the biological functions of the helix-loop-helix Id3 protein, we have examined the effects of ectopic modulation of Id3 expression on in vitro induced differentiation of mouse C2C12 myoblast cells. Transient and stable C2C12 transfectants expressing either inducible or constitutive levels of exogenous Id3 were impaired in their ability to differentiate in response to removal of mitogenic serum growth factors. Stable Id3 transfectants displayed an enhanced proliferative capacity associated with a delay in exit from the cell cycle in response to differentiation induction. Antisense blockade of Id3 potentiated differentiation and exit from S phase of the cell cycle. These observations suggest that Id3 functions as a negative regulator of differentiation by integrating mitogenic growth factor signaling into the gene regulatory program maintaining cell cycle progression.
Atherton
G T
GT
CRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Travers
H
H
Deed
R
R
Norton
J D
JD
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D018257:Helix-Loop-Helix Motifs; D051796:Inhibitor of Differentiation Proteins; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection
D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; C075640:ID3 protein, human