BTG1: a triiodothyronine target involved in the myogenic influence of the hormone.
The product of the B-cell translocation gene 1 (BTG1), a member of an antiproliferative protein family including Tis-21/PC3 and Tob, is thought to play an important role in the regulation of cell cycle progression. We have shown in a previous work that triiodothyronine (T3) stimulates quail myoblast differentiation, partly through a cAMP-dependent mechanism involved in the stimulation of cell cycle withdrawal. Furthermore, we found that T3 or 8-Br-cAMP increases BTG1 nuclear accumulation in confluent myoblast cultures. In this study, we report that BTG1 is essentially expressed at cell confluence and in differentiated myotubes. Whereas neither T3 nor cAMP exerted a direct transcriptional control upon BTG1 expression, we found that AP-1 activity, a crucial target involved in the triiodothyronine myogenic influence, repressed BTG1 expression, thus probably explaining the low BTG1 expression level in proliferating myoblasts. In transient transfection studies, we demonstrated that an AP-1-like sequence located in the BTG1 promoter was involved in this negative regulation. Our present data also bring evidence that the stimulation of BTG1 nuclear accumulation by T3 or 8-Br-cAMP probably results from an increased nuclear import or retention in the nucleus. Lastly, BTG1 overexpression in quail myoblasts mimicked the T3 or 8-Br-cAMP myogenic influence: (i) inhibition of myoblast proliferation due to an increased rate of myoblast withdrawal from the cell cycle; and (ii) stimulation of terminal differentiation. These data suggest that BTG1 is probably involved in T3 and cAMP myogenic influences. In conclusion, BTG1 is a T3 target involved in the regulation of myoblast differentiation.
Rodier
A
A
Laboratoire Différenciation Cellulaire et Croissance, INRA, 2 Place Viala, Montpellier Cedex 1, 34060, France.
Marchal-Victorion
S
S
Rochard
P
P
Casas
F
F
Cassar-Malek
I
I
Rouault
J P
JP
Magaud
J P
JP
Mason
D Y
DY
Wrutniak
C
C
Cabello
G
G
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018482:Muscle, Skeletal; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011784:Quail; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*
D018006:Myogenic Regulatory Factors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014284:Triiodothyronine; D015124:8-Bromo Cyclic Adenosine Monophosphate