Involvement of BTBD1 in mesenchymal differentiation.
BTBD1 is a recently cloned BTB-domain-containing protein particularly expressed in skeletal muscle and interacting with DNA topoisomerase 1 (Topo1), a key enzyme of cell survival. We have previously demonstrated that stable overexpression of a N-terminal truncated BTBD1 inhibited ex vivo myogenesis but not adipogenesis of pluripotent C2C12 cells. Here, BTBD1 expression was studied in three models of cellular differentiation: myogenesis (C2C12 cells), adipogenesis (3T3-L1 cells) and osteogenesis (hMADS cells). BTBD1 mRNA was found to be upregulated during myogenesis. At the opposite, we have not observed BTBD1 upregulation in an altered myogenesis cellular model and we observed a downregulation of BTBD1 mRNA expression in adipogenesis. Interestingly, amounts of Topo1 protein, but not Topo1 mRNA, were found to be modulated at the opposite of BTBD1 mRNA. No variation of BTBD1 expression was measured during osteogenesis. Taken together, these results indicate that BTBD1 mRNA is specifically regulated during myogenic and adipogenic differentiation, in relation with Topo1 expression. Moreover, they corroborate observations made previously with truncated BTBD1 and show that BTBD1 is a key protein of balance between adipogenesis and myogenesis. Finally, a transcriptome analysis gave molecular clues to decipher BTBD1 role, with an emphasis on the involvement in ubiquitin/proteasome degradation pathway.
Pisani
Didier F
DF
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Faculté des Sciences, Parc Valrose, Nice, France.
Coldefy
Anne-Sophie
AS
Elabd
Christian
C
Cabane
Candice
C
Salles
Jerome
J
Le Cunff
Martine
M
Derijard
Benoit
B
Amri
Ez-Zoubir
EZ
Dani
Christian
C
Leger
Jean J
JJ
Dechesne
Claude A
CA
D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism
C522053:BTBD1 protein, mouse; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D004264:DNA Topoisomerases, Type I