HGNC Approved Gene Symbol: LIMD1
Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38) : 3:45,594,751-45,686,341 (from NCBI)
Interstitial deletions of the short arm of chromosome 3 are found in a large number of tumors. By comparative genomic hybridization, deletions of 3p are frequently detected in breast, cervix, bladder, renal cell, and small cell lung carcinomas. Microscopically detectable interstitial deletions of 3p21 are found in a variety of tumors. Loss of heterozygosity studies have shown frequent deletions of the 3p21.3 region in carcinomas of lung, kidney, head and neck, breast, and bladder. Following up on these strong suggestions of the presence of 1 or more tumor suppressor genes on 3p, Szeles et al. (1997) used an experimental system, the elimination test, to identify a 1-Mb segment, referred to as the chromosome 3 common eliminated region-1, or C3CER1. C3CER1 was also covered by a PAC contig. Using the sequence of 2 overlapping PACs from C3CER1, Kiss et al. (1999) localized the cDNA encoding the precursor of mitochondrial leucyl-tRNA synthetase (LARS2; 604544). They also characterized a novel human LIM domain-containing gene, LIMD1, and its mouse ortholog. LIM domains consist of a cysteine-rich consensus sequence containing 2 distinct zinc-binding subdomains, which mediate protein-protein interactions. The predicted protein sequences of the human and mouse genes show 3 LIM domains located at the C-terminal end, indicating that these genes belong to group 3 of the gene family encoding the LIM motifs. The predicted human LIMD1 protein contains 676 amino acids. Northern blot analysis indicated that both the mouse and human genes are ubiquitously expressed, with human LIMD1 being expressed predominantly as a 7.5-kb transcript. The LIM motif had been previously identified in many developmentally important factors from various eukaryotes. These factors had been shown to play a role in intracellular signaling, transcriptional regulation, and cellular differentiation during development. Thus, the C3CER1-located LIMD1 gene deserves further study for its possible role in tumor suppression.
By immunofluorescence microscopy of a human osteoblast cell line, Sharp et al. (2004) localized LIMD1 predominantly to the cytoplasm, with strongest staining in a punctate perinuclear distribution. Some LIMD1 localized to the nucleus, but not to nucleoli. Using a nuclear export blocker, Sharp et al. (2004) showed that LIMD1 shuttles between the cytoplasm and nucleus.
Sharp et al. (2004) found that LIMD1 specifically interacted with the retinoblastoma protein (RB1; 614041) in HeLa cells, and the interaction required amino acids 404 through 442, just prior to the 3 C-terminal LIM domains. The interaction between LIMD1 and RB1 inhibited E2F (see E2F1; 189971)-mediated transcription and suppressed expression of a majority of genes with E2F1-responsive elements. LIMD1 blocked tumor growth in vitro and in vivo, and was downregulated in a majority of human lung cancer samples examined.
Kiss et al. (1999) characterized the genomic structure of the human LIMD1 gene and found that the coding region of LIMD1 contains 8 exons.
By FISH, Kiss et al. (1999) mapped the LIMD1 gene to 3p21. They assigned the mouse homolog to the chromosome 9F subtelomeric region using FISH.
Kiss, H., Kedra, D., Yang, Y., Kost-Alimova, M., Kiss, C., O'Brien, K. P., Fransson, I., Klein, G., Imreh, S., Dumanski, J. P. A novel gene containing LIM domains (LIMD1) is located within the common eliminated region 1 (C3CER1) in 3p21.3. Hum. Genet. 105: 552-559, 1999. [PubMed: 10647888] [Full Text: https://doi.org/10.1007/s004399900188]
Sharp, T. V., Munoz, F., Bourboulia, D., Presneau, N., Darai, E., Wang, H.-W., Cannon, M., Butcher, D. N., Nicholson, A. G., Klein, G., Imreh, S., Boshoff, C. LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription. Proc. Nat. Acad. Sci. 101: 16531-16536, 2004. [PubMed: 15542589] [Full Text: https://doi.org/10.1073/pnas.0407123101]
Szeles, A., Yang, Y., Sandlund, A. M., Kholodnyuck, I., Kiss, H., Kost-Alimova, M., Zabarovsky, E. R., Stanbridge, E., Klein, G., Imreh, S. Human/mouse microcell hybrid based on elimination test reduces the putative tumor suppressor region at 3p21.3 to 1.6 cM. Genes Chromosomes Cancer 20: 329-336, 1997. [PubMed: 9408748]