Alternative titles; symbols
HGNC Approved Gene Symbol: TGIF2
Cytogenetic location: 20q11.23 Genomic coordinates (GRCh38) : 20:36,573,464-36,593,950 (from NCBI)
Homeodomain transcription factors play fundamental roles in directing cellular proliferation and differentiation and in determining cell fates. TGIF2 is a member of a subfamily of transcription factors with an atypical homeodomain called a TALE (3-amino acid loop extension) that inserts 3 amino acids between helices 1 and 2 of the homeodomain (Imoto et al., 2000).
By searching an EST database using TGIF (602630) as the query, followed by RT-PCR of an ovarian cancer cell line, Imoto et al. (2000) obtained a full-length cDNA encoding TGIF2. The deduced 237-amino acid protein has a calculated molecular mass of about 30 kD and contains a TALE sequence. It also has a repression domain containing a proline-rich region that is a putative SH3 domain-binding site and is thought to be involved in transcriptional regulation. The homeodomain of TGIF2 is 77% identical to the corresponding domain within TGIF, but outside this domain the similarity is only 49%. Northern blot analysis revealed ubiquitous expression of a single transcript, with highest levels in heart, kidney, and testis, and lowest levels in brain and prostate. Transfection of COS-7 cells with fluorescence-tagged TGIF2 revealed localization in the cell nucleus but exclusion from nucleoli.
Imoto et al. (2000) noted that chromosome 20q, where the TGIF2 gene maps, is often amplified in ovarian cancers. They screened 14 ovarian cancer cell lines for amplification and expression of the TGIF2 gene and detected overexpression in 5 cell lines. These lines also showed amplification by FISH analysis, with the mean copy numbers ranging from 4 to 8. All cell lines with low levels of TGIF2 expression showed no increase in relative copy numbers.
Imoto et al. (2000) determined that the TGIF2 gene contains 3 exons and spans about 18 kb.
By FISH, Imoto et al. (2000) mapped the TGIF2 gene to chromosome 20q11.2-q12.
The article by Krzeszinski et al. (2014) identifying TGIF2 as an essential MIR34A (611172) target that is pro-osteoclastogenic was retracted because the integrity of the bone histomorphometry data was called into question.
Imoto, I., Pimkhaokham, A., Watanabe, T., Saito-Ohara, F., Soeda, E., Inazawa, J. Amplification and overexpression of TGIF2, a novel homeobox gene of the TALE superclass, in ovarian cancer cell lines. Biochem. Biophys. Res. Commun. 276: 264-270, 2000. [PubMed: 11006116] [Full Text: https://doi.org/10.1006/bbrc.2000.3449]
Krzeszinski, J. Y., Wei, W., Huynh, H., Jin, Z., Wang, X., Chang, T.-C., Xie, X.-J., He, L., Mangala, L. S., Lopez-Berestein, G., Sood, A. K., Mendell, J. T., Wan, Y. miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature 512: 431-435, 2014. Note: Erratum: Nature 570: E51, 2019. Retraction: Nature 582: 134 only, 2020. [PubMed: 25043055] [Full Text: https://doi.org/10.1038/nature13375]