A follistatin-like gene, mac25, may act as a growth suppressor of osteosarcoma cells.
mac25, a retinoic acid-inducible gene that is expressed at high levels in senescent epithelial cells, was initially cloned as a gene that is differentially expressed in meningioma. Although the homology of its product with members of family of insulin-like growth factor-binding proteins was suggested, the product also exhibits strong homology to follistatin, an activin-binding protein. However, a domain corresponding to the carboxyl terminus of follistatin is not found in mac25. The carboxyl-terminally truncated form of follistatin, generated by alternative splicing, has stronger activin-binding activity than the complete form. This result suggests that mac25 might act as an activated follistatin. Clonal growth of a p53-deficient osteosarcoma cell line was strongly inhibited when the murine mac25 gene, as well as the p53 gene, was introduced. Resembling activins that belong to the transforming growth factor-beta (TGF-beta) superfamily, mac25 and p53 might associate with similar but distinct targets, namely cyclin-dependent kinase inhibitors. However, there is no evidence for compensation of p53 function by mac25 in the development of p53-deficient mice, as judged from the pattern of expression of mac25 in mice. mac25 might act as a tumor suppressor, modulating signaling of the TGF-beta family, as does alpha-inhibin.
Kato
M V
MV
Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Sato
H
H
Tsukada
T
T
Ikawa
Y
Y
Aizawa
S
S
Nagayoshi
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D038681:Follistatin; D016147:Genes, Tumor Suppressor; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D017386:Sequence Homology, Amino Acid
D038681:Follistatin; D006023:Glycoproteins