Induction of apoptosis and inhibition of cell growth by developmental regulator hTBX5.
T box (Tbx) genes are a large family of transcription regulators that play critical roles in invertebrate and vertebrate development. Mutations in Tbx5 gene have been found to cause Holt-Oram syndrome (HOS) in humans. Partial dysfunction of TBX5 in mouse also causes HOS phenotype. Little is known about its molecular and cellular mechanism. Here, we report that ectopic expression of TBX5 inhibited colony formation, induced apoptosis, and decreased the growth rate of cells. The two point mutations in T domain and a truncated mutation in C-terminal found in human HOS patients produced TBX5 mutant proteins with a significantly reduction of colony suppression activity. Deletion of the DNA-binding domain, however, nearly completely abrogated its ability to suppress colony formation. These results reveal TBX5 as a new regulator of apoptosis and cell growth, suggesting a possible mechanism for Holt-Oram syndrome, and a potential reagent for controlling tumor growth.
He
Ming-Liang
ML
Institute of Molecular Biology, Open Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, SAR, China. mlhe@hkucc.hku.hk
Chen
Ying
Y
Peng
Ying
Y
Jin
Dadao
D
Du
Dan
D
Wu
Jun
J
Lu
Ping
P
Lin
Marie C
MC
Kung
Hsiang-Fu
HF
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D009154:Mutation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5