Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2–q21.3

Hanaoka, Eiji; Ozaki, Toshinori; Ohira, Miki; Nakamura, Yohko; Suzuki, Mikio; Takáhashi, Eiichi; Moriya, Hideshige; Nakagawara, Akira; Sato, Shigeru

doi:10.1007/s100380050209

Cited by 3 publications

(6 citation statements)

References 14 publications

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“…Finally, it can be also appreciated in that figure that many among the samples with the highest total levels of expression, obtained adding together all ubiquilin genes, come from the nervous system (see e. g. hypothalamus, cerebral cortex, cerebellum, etc.) in good agreement with previous data [6,11]. …”

Section: Resultssupporting

confidence: 93%

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The ubiquilin gene family: evolutionary patterns and functional insights

Marı́n

2014

BMC Evol Biol

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BackgroundUbiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood.ResultsIn this study, evolutionary and functional data are combined to determine the origin and diversification of the ubiquilin gene family and to characterize novel potential roles of ubiquilins in mammalian species, including humans. The analysis of more than six hundred sequences allowed characterizing ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. fungi, many animals) have single ubiquilin genes, but duplications in animal, plant, alveolate and excavate species are described. Seven different ubiquilins have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, had not been hitherto described. Significantly, marsupial and eutherian mammals have the most complex ubiquilin gene families, composed of up to 6 genes. This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis. A gene with related features has independently arisen in species of the Drosophila genus. Positive selection acting on some mammalian ubiquilins has been detected.ConclusionsThe ubiquilin gene family is highly conserved in eukaryotes. The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues.

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Section: Resultssupporting

confidence: 93%

“…On one hand, UBQLN1 is broadly expressed, but no particularly low expression in testis in detected (this is clearly seen in Figure 7). This is probably a real result, given that a relatively high level of expression in testis was observed before [11]. On the other hand, expression in whole brain samples for UBQLN4 appears as one of the lowest.…”

Section: Resultsmentioning

confidence: 55%

The ubiquilin gene family: evolutionary patterns and functional insights

Marı́n

2014

BMC Evol Biol

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“…24) In their experimental systems, the overall levels of CDK2 and p27 kip1 did not change upon treatment with VP16, though there was a significant , that can bind to cyclin A and inhibit the degradation of cyclin A. 9) XDRP1 showed marked sequence homology with DA41 7) and overexpression of XDRP1 in frog embryos blocked embryonic cell division.…”

Section: Discussionmentioning

confidence: 92%

“…6) Additionally, we have reported that human DA41 was mapped to chromosome 9q21.2-q21.3, a position overlapping the candidate tumor suppressor locus for bladder cancer. 7) A recent search of the databases for DA41-related protein(s) identified mouse PLIC-1, PLIC-2, frog XDRP1 and yeast DSK2. [7][8][9][10] PLIC-1 and PLIC-2 interact with the cytoplasmic tail of integrin-associated protein (IAP) and mediate the interaction between IAP and vimentin-containing intermediate filaments.…”

mentioning

confidence: 99%

“…7) A recent search of the databases for DA41-related protein(s) identified mouse PLIC-1, PLIC-2, frog XDRP1 and yeast DSK2. [7][8][9][10] PLIC-1 and PLIC-2 interact with the cytoplasmic tail of integrin-associated protein (IAP) and mediate the interaction between IAP and vimentin-containing intermediate filaments. 8) On the other hand, XDRP1 associates with the NH 2 -terminal region of cyclin A and inhibits the degradation of cyclin A.…”

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confidence: 99%

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Overexpression of DA41 in v‐Ha‐ras‐3Y1 Cells Causes Growth Suppression

Ozaki

Nakamura

Hanaoka

et al. 2000

Japanese Journal of Cancer Research

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We have recently found that DA41 exhibits marked homology with mouse PLIC-1, PLIC-2, frog XDRP1 and yeast DSK2. XDRP1 has been shown to be associated with cyclin A, and blocks cell division of frog embryo. In the present study, we examined the biological role(s) of DA41 in mammalian cells by overexpressing it in v-Ha-ras-transformed 3Y1 cells (ras-3Y1). Transfectants which expressed a high level of DA41 mRNA exhibited a decrease in growth rate, a reduction in saturation density, and a suppression of colony formation in soft agar medium. To clarify the molecular mechanism(s) by which DA41 affects cell growth, the effect of DA41 expression on the levels of various cell cycle-regulatory proteins was examined. The forced expression of DA41 gene resulted in a remarkable reduction in CDK2 activity, while the amount of CDK2 did not change. These observations indicate that DA41 is involved in cell cycle regulation in ras-3Y1 cells.Key words: DA41 -Growth suppression -ras -3Y1We have previously shown that rat DAN protein suppresses the malignant phenotypes of v-src-transformed 3Y1 cells (SR-3Y1) and also negatively regulates cell cycle progression at the G1/S boundary.1, 2) DAN is a secreted glycoprotein 3, 4) with a characteristic cysteine-knot structure common to the DAN/Cerberus family, which includes Gremlin/Drm. 5) Injection studies in frog embryos have suggested that the DAN/Cerberus family acts as an antagonist regulating BMP signalling. 5)DA41 was initially identified as a novel cytoplasmic protein which can associate with DAN by means of yeast two-hybrid screening of a normal rat lung cDNA library. 6)The interaction between DAN and DA41 is mediated through the NH 2 -terminal domain and the cysteine-knot region of DAN. The expression of DA41 gene was ubiquitous in adult rat tissues. Interestingly, the amount of DA41 mRNA started to increase at the late G1 phase and the same level was maintained until the onset of the S phase of the cell cycle, raising the possibility that DA41 might have some regulatory role(s) in cell cycle progression. 6)Additionally, we have reported that human DA41 was mapped to chromosome 9q21.2-q21.3, a position overlapping the candidate tumor suppressor locus for bladder cancer. 7)A recent search of the databases for DA41-related protein(s) identified mouse PLIC-1, PLIC-2, frog XDRP1 and yeast DSK2.7-10) PLIC-1 and PLIC-2 interact with the cytoplasmic tail of integrin-associated protein (IAP) and mediate the interaction between IAP and vimentin-containing intermediate filaments.8) On the other hand, XDRP1 associates with the NH 2 -terminal region of cyclin A and inhibits the degradation of cyclin A.9) Microinjection of recombinant XDRP1 into fertilized frog eggs blocked the cell division, suggesting a cell cycle-regulatory role of XDRP1.9) Furthermore, overproduction of DSK2 induced a mitotic defect with a short spindle. 10)In the present study, we examined the role(s) of DA41 in mammalian cells by overexpressing it in v-Ha-rastransformed 3Y1 cells (ras-3Y1). As described previously, the e...

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Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

et al. 2021

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Ubiquilin-1 (UBQLN1) is an essential factor for the maintenance of proteostasis in cells. It is important for the regulation of different protein degradation mechanisms, including the ubiquitin-proteasome system, autophagy and endoplasmic reticulum-associated protein degradation pathways. However, the role of UBQLN1 in cancer progression remains largely unknown. In the present study, the expression, functions and molecular mechanisms of UBQLN1 in breast cancer tissue samples and cell lines were explored. Immunohistochemical and bioinformatics analyses revealed that UBQLN1 expression was significantly upregulated in breast cancer tissues and cell lines. UBQLN1 expression in breast cancer was significantly associated with lymph node metastasis and TNM stage. Moreover, a high UBQLN1 expression was a predictor of an unfavorable survival in patients with breast cancer. In vitro, UBQLN1 silencing markedly inhibited cell migration and invasion, epithelial-to-mesenchymal transition (EMT) and MMP expression. UBQLN1 silencing attenuated the stem cell-like properties of breast cancer cells, including their mammosphere-forming abilities. UBQLN1 knockdown also enhanced breast cancer cell chemosensitivity to paclitaxel. The expression levels of the stem cell markers.Aldehyde dehydrogenase 1 (ALDH1), Oct-4 and Sox2 were significantly decreased in the cells in which UBQLN1 was silenced, whereas breast cancer stem cells exhibited an increased expression of UBQLN1. Mechanistically, UBQLN1 knockdown inhibited the activation of AKT signaling, as revealed by the increased PTEN expression and the decreased expression of phosphorylated AKT in cells in which UBQLN1 was silenced. On the whole, the present study demonstrates that UBQLN1 is aberrantly upregulated in breast cancer and predicts a poor prognosis. The silencing of UBQLN1 inhibited the invasion, EMT and stemness of breast cancer cells, possibly via AKT signaling.

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Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2–q21.3

Cited by 3 publications

References 14 publications

The ubiquilin gene family: evolutionary patterns and functional insights

The ubiquilin gene family: evolutionary patterns and functional insights

Overexpression of DA41 in v‐Ha‐ras‐3Y1 Cells Causes Growth Suppression

Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

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