Identification and Characterization of an Inner Ear-Expressed Human Melanoma Inhibitory Activity (MIA)-like Gene (MIAL) with a Frequent Polymorphism That Abolishes Translation

Rendtorff, Nanna Dahl; Frödin, Morten; Attié‐Bitach, Tania; Vekemans, Michel; Tommerup, Niels

doi:10.1006/geno.2000.6409

Cited by 22 publications

(18 citation statements)

References 39 publications

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“…Recently, the extracellular protein OTOR, which has a high sequence identity and similarity to the human MIA protein, has been described [1][2][3]. Due to the high levels of sequence identity and similarity between MIA and OTOR we predict that OTOR also adopts an SH3 domain-like structure (Figs.…”

Section: Family Of Extracellular Sh3-domainsmentioning

confidence: 95%

“…In the year 2000, a novel gene, OTOR (other designations: FDP (fibrocyte-derived protein), MIAL (MIA-Like)), was cloned by two experimental strategies and shown to be a close homologue of MIA [1][2][3]. Cohen-Salmon et al identified OTOR via subtractive cDNA screening in search for genes which are preferentially expressed in the inner ear.…”

Section: The Mia Protein Familymentioning

confidence: 98%

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Extracellular SH3 Domain Containing Proteins – Features of a New Protein Family

Stoll

Bosserhoff

2008

CPPS

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In the year 1994, the protein MIA (melanoma inhibitory activity) was found to be strongly expressed and secreted by malignant melanomas and subsequent studies revealed that MIA has an important function in melanoma development and invasion. Multidimensional NMR-spectroscopy and x-ray crystallography revealed that recombinant human MIA adopts a Src homology 3 (SH3) domain-like fold in solution, a structure with two perpendicular antiparallel three- and five-stranded beta-sheets. SH3 domains are protein modules that are found in many intracellular signalling proteins and mediate protein-protein interactions by binding to proline-rich peptide sequences. Unlike previously described protein structures with SH3 domain folds, MIA is a secreted single-domain protein of 12 kDa that contains an additional antiparallel beta-sheet and two disulfide bonds. Furthermore, the charge surrounding the canonical binding site differs from that of classical SH3 domains. The two disulfide bonds are crucial for correct folding and function as revealed by mutation analysis. Therefore, MIA appears to be the first extracellular protein adopting an SH3 domain-like fold. MIA was shown to interact with fibronectin, and MIA-interacting peptide ligands identified by phage display screening are similar to the consensus sequence of type III human fibronectin repeats, especially FN14. Interestingly, recent data revealed that MIA can also directly bind to integrin alpha 4 beta 1 and alpha 5 beta1 and that it modulates integrin activity negatively. These findings suggest an interesting role of the SH3-domain proteins in the extracellular compartment. Recently, MIA homologous proteins with a sequence identity of 44% and a sequence homology of approximately 80% were determined (TANGO, MIA-2, OTOR). This clearly suggests that this structural device is used more frequently, in processes ranging from developmental changes to the interference of cell attachment in the extracellular matrix. Detailed studies are necessary to determine the exact function of the MIA homologous proteins. It will be interesting to know whether additional protein families can be identified which are secreted and carry SH3 domain-like modules, in addition to elucidate what the specific physiological targets of this protein family are.

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Section: Family Of Extracellular Sh3-domainsmentioning

confidence: 95%

Section: The Mia Protein Familymentioning

confidence: 98%

Extracellular SH3 Domain Containing Proteins – Features of a New Protein Family

Stoll

Bosserhoff

2008

CPPS

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“…The protein MIA, which is strongly expressed in melanoma cells but not in melanocytes, is likely to represent a key molecule regulating melanoma progression (5,6). In 2000 OTOR [other designations: fibrocyte-derived protein (FDP), MIA-like (MIAL)], was cloned and shown to be a close homologue of MIA (7)(8)(9). Cohen-Salmon et al (7) identified OTOR via subtractive cDNA screening in a search for genes which are referentially expressed in the inner ear.…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of TANGO in colon and hepatocellular carcinomas

Arndt

Boßerhoff²

2007

Oncol Rep

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Abstract. The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

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“…In accordance with their role in ionic and water transport, fibrocytes express various combinations of ion and water channels, carbonic anhydrases II and III (3,21,25,27,30), as well as gap junction connexins 26, 30, and 31 (7, 12, 37). The findings that fibrocytes also express extracellular matrix proteins (15,33,35) and proteins involved in cell-cell signaling, such as bone and cartilage morphogens (2,18,20,31) and the inner ear-specific cochlin, whose function is unknown (19), indicate a broader role and probably a diversity of specific functions that remain to be elucidated. The fact that the alteration of the fibrocyte integrity leads to pathology is an indication of their importance in inner ear physiology.…”

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confidence: 99%

Deafness and Cochlear Fibrocyte Alterations in Mice Deficient for the Inner Ear Protein Otospiralin

Delprat

Ruel

Guitton

et al. 2005

Molecular and Cellular Biology

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In the cochlea, the mammalian auditory organ, fibrocytes of the mesenchymal nonsensory regions play important roles in cochlear physiology, including the maintenance of ionic and hydric components in the endolymph. Occurrence of human deafness in fibrocyte alterations underlines their critical roles in auditory function. We recently described a novel gene, Otos, which encodes otospiralin, a small protein of unknown function that is produced by the fibrocytes of the cochlea and vestibule. We now have generated mice with deletion of Otos and found that they show moderate deafness, with no frequency predominance. Histopathology revealed a degeneration of type II and IV fibrocytes, while hair cells and stria vascularis appeared normal. Together, these findings suggest that impairment of fibrocytes caused by the loss in otospiralin leads to abnormal cochlear physiology and auditory function. This moderate dysfunction may predispose to age-related hearing loss.Within the cochlea, the mammalian auditory organ, mesenchymal nonsensory regions (i.e., the spiral limbus proximal to the cochlear axis and the spiral ligament forming the lateral wall of the cochlea) contain fibrocytes that play important roles in cochlear physiology. In the spiral ligament, these fibrocytes form distinct groups according to their location, morphological appearance, and marker expression, which suggest their functional specialization (26). Thus, the circumferentially oriented type III fibrocytes lining the otic capsule and the spindleshaped type IV fibrocytes lateral to the basilar membrane package the cochlear content and buffer mechanical constraints generated by sound vibrations (8). The type I fibrocytes (behind the stria vascularis), tightly packed with collagen bundles, shape the curvature of the lateral wall. Type II fibrocytes (below the stria vascularis) and type V fibrocytes (above the stria vascularis) are rich in mitochondria and form many interdigitating processes, indicating high metabolic and exchange activities. Type I, II, and V fibrocytes and basal and intermediate cells of the stria vascularis are all interconnected with gap junctions (10). This gap-junctioned network is postulated to be involved in ion and water circulation, including potassium recycling (34). Potassium is indeed central to the cochlear physiology, since it is the charge-carrying ion for the sensory transduction. It is secreted by the marginal cells of the stria vascularis to maintain a very high concentration (150 mM) in the endolymph, the extracellular fluid bathing hair cell stereocilia. Recycling of potassium though the fibrocyte network is one of several processes that provide potassium to intermediate cells of the stria vascularis (28, 34). This permanent flux of potassium cycling in the cochlea generates the so-called "endocochlear potential " (ϩ85 mV), which gives the main driving force for potassium entry into the sensory hair cell.Progress in the functional characterization of the cochlear fibrocytes has been made with the discovery of proteins exp...

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Identification and Characterization of an Inner Ear-Expressed Human Melanoma Inhibitory Activity (MIA)-like Gene (MIAL) with a Frequent Polymorphism That Abolishes Translation

Cited by 22 publications

References 39 publications

Extracellular SH3 Domain Containing Proteins – Features of a New Protein Family

Extracellular SH3 Domain Containing Proteins – Features of a New Protein Family

Reduced expression of TANGO in colon and hepatocellular carcinomas

Deafness and Cochlear Fibrocyte Alterations in Mice Deficient for the Inner Ear Protein Otospiralin

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