Alternative titles; symbols
HGNC Approved Gene Symbol: TRIM29
Cytogenetic location: 11q23.3 Genomic coordinates (GRCh38) : 11:120,111,286-120,138,113 (from NCBI)
Kapp et al. (1992) cloned ATDC, a candidate gene for ataxia-telangiectasia (AT; 208900) that maps to the region of chromosome 11q23 containing the AT locus. They rescued integrated cosmid sequences that partially restored resistance to ionizing radiation in an AT cell line of complementation group D and, by screening a HeLa cell cDNA library, obtained an ATDC cDNA. RNA blot analysis detected ATDC transcripts of 1.8, 2.6, 3.0, 4.7, and 5.7 kb that were variably expressed among different cell lines. The 3.0-kb transcript, which corresponds to the cDNA isolated from HeLa cells, was the most abundant transcript in HeLa cells. Southern blot analysis indicated that ATDC is a single-copy gene in the human genome.
Leonhardt et al. (1994) characterized the 3.0-kb ATDC cDNA isolated from HeLa cells (Kapp et al., 1992). The deduced 588-amino acid protein contains 2 conserved zinc finger motifs and an adjacent leucine zipper motif. A rare 2.9-kb cDNA with a different exon 3 splice site encodes a protein lacking 34 amino acids at the end of the leucine zipper region.
Using a B-box domain consensus sequence to screen EST databases for novel TRIM family members, Reymond et al. (2001) identified and cloned mouse and human TRIM29. The deduced proteins contain type-1 and type-2 B-box domains and a coiled-coil region. Northern blot analysis detected a 3-kb transcript in placenta, prostate, and thymus. In a human teratocarcinoma cell line, TRIM29 localized to filamentous cytoplasmic structures.
Brzoska et al. (1995) found that the ATDC protein physically interacted with the intermediate filament protein vimentin (193060), a protein kinase C (176960) substrate and colocalizing protein, and with an inhibitor of protein kinase C, PKCI1 (601314). Indirect immunofluorescence analysis of cultured cells transfected with a plasmid encoding epitope-tagged ATDC localized the protein to vimentin filaments. Brzoska et al. (1995) suggested that the ATDC and PKCI1 proteins may be components of a single transduction pathway that is induced by ionizing radiation and mediated by protein kinase C. The fact that the ATM gene (607585) encodes a protein with a putative phosphatidylinositol 3-kinase domain and functions as a lipid-mediated signaling molecule is consistent with a model in which ATDC and PKC function downstream from ATM in this pathway.
Using a yeast 2-hybrid assay and coimmunoprecipitation experiments, Reymond et al. (2001) showed that TRIM29 could form higher order homomeric complexes. The coiled-coil region of TRIM29 was indispensable for formation of high molecular mass complexes and for the specific intracellular localization of TRIM29.
Using Northern blot analysis, Hosoi et al. (2006) detected no ATDC transcript in 4 of 11 tumor cell lines, and using Western blot analysis, they detected no ATDC protein in 8 of these cell lines. Transfection of ATDC into 2 tumor cell lines lacking ATDC mRNA and protein expression suppressed colony formation in soft agar, suggesting that suppressed ATDC expression is associated with malignant phenotype.
Using quantitative RT-PCR and immunoblot analyses, Dou et al. (2019) showed that Trim29 expression was induced in mouse NK cells in response to stimulation by Il12 (see 161560) and Il18 (600953). Conditional deletion of Trim29 in mouse NK cells promoted production of Ifn-gamma (147570) in activated NK cells and enhanced host defense against virus infection, indicating that Trim29 negatively regulated expression of Ifn-gamma and inhibited NK functions. Production of Ifn-gamma in NK cells was dynamic and correlated with Tab2 (605101) expression. Deletion of Trim29 also stimulated expression of Tab2 in activated NK cells in mice, as Trim29 and Tab2 interacted through their respective C terminus and N terminus, and Trim29 induced Tab2 degradation by ubiquitination via K48 linkage.
Leonhardt et al. (1994) determined that the coding region of the ATDC gene contains a least 9 exons.
By sequencing a cosmid clone associated with ATDC, Kapp et al. (1992) mapped the ATDC gene to the region between THY1 (188230) and D11S83 on chromosome 11q23. Using radiation hybrid analysis, Reymond et al. (2001) mapped the TRIM29 gene to chromosome 11q22-q23.
In mice expressing the Kras (190070) G12D mutation, known to cause pancreatic tumorigenesis, Wang et al. (2019) conditionally ablated pancreas-specific Atdc expression and termed these mice KPCYA -/-. Ablation of Atdc did not affect pancreatic development and morphology, and KPCYA -/- mice were born at expected mendelian ratios and were phenotypically normal at birth. KPCYA -/- mice did not develop pancreatic adenocarcinoma (PDA) and had prolonged survival compared with controls. In Kras(G12D) Atdc-expressing mice, Atdc was upregulated in acinar cells during Kras G12D-induced formation of acinar-ductal metaplasia (ADM), and Atdc was required for progression of ADM to pancreatic intraepithelial neoplasia. Atdc promoted Kras G12D-induced ADM by upregulating Sox9 (608160) expression through activating beta-catenin (116806) signaling. As a result, knockout of Atdc resulted in downregulation of Sox9 and inhibited Kras G12D-induced ADM. Wang et al. (2019) found that, in support of these results, expression of ATDC, beta-catenin, and SOX9 was increased in ADM lesions and PDA in the pancreatic tissue of human patients.
Brzoska, P. M., Chen, H., Zhu, Y., Levin, N. A., Disatnik, M.-H., Mochly-Rosen, D., Murnane, J. P., Christman, M. F. The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. Proc. Nat. Acad. Sci. 92: 7824-7828, 1995. [PubMed: 7644499] [Full Text: https://doi.org/10.1073/pnas.92.17.7824]
Dou, Y., Xing, J., Kong, G., Wang, G., Lou, X., Xiao, X., Vivier, E., Li, X. C., Zhang, Z. Identification of the E3 ligase TRIM29 as a critical checkpoint regulator of NK cell functions. J. Immun. 203: 873-880, 2019. [PubMed: 31270148] [Full Text: https://doi.org/10.4049/jimmunol.1900171]
Hosoi, Y., Kapp, L. N., Murnane, J. P., Matsumoto, Y., Enomoto, A., Ono, T., Miyagawa, K. Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC. Biochem. Biophys. Res. Commun. 348: 728-734, 2006. [PubMed: 16890201] [Full Text: https://doi.org/10.1016/j.bbrc.2006.07.115]
Kapp, L. N., Painter, R. B., Yu, L.-C., van Loon, N., Richard, C. W., III, James, M. R., Cox, D. R., Murnane, J. P. Cloning of a candidate gene for ataxia-telangiectasia group D. Am. J. Hum. Genet. 51: 45-54, 1992. [PubMed: 1609804]
Leonhardt, E. A., Kapp, L. N., Young, B. R., Murnane, J. P. Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia group D (ATDC). Genomics 19: 130-136, 1994. [PubMed: 8188213] [Full Text: https://doi.org/10.1006/geno.1994.1022]
Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A. The tripartite motif family identifies cell compartments. EMBO J. 20: 2140-2151, 2001. [PubMed: 11331580] [Full Text: https://doi.org/10.1093/emboj/20.9.2140]
Wang, L., Yang, H., Zamperone, A., Diolaiti, D., Palmbos, P. L., Abel, E. V., Purohit, V., Dolgalev, I., Rhim, A. D., Ljungman, M., Hadju, C. H., Halbrook, C. J., Bar-Sagi, D., Pasca di Magliano, M., Crawford, H. C., Simeone, D. M. ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis. Genes Dev. 33: 641-655, 2019. [PubMed: 31048544] [Full Text: https://doi.org/10.1101/gad.323303.118]