FIP-2, an IκB-Kinase-γ-Related Protein, Is Associated with the Golgi Apparatus and Translocates to the Marginal Band during Chicken Erythroblast Differentiation

Stroissnigg, Heike; Repitz, Marion; Miloloza, Angelina; Linhartová, Irena; Beug, Hartmut; Wiche, Gerhard; Propst, Friedrich

doi:10.1006/excr.2002.5567

Cited by 20 publications

(15 citation statements)

References 38 publications

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“…We also show that the punctate OPTN staining is not distinctly associated with the Golgi apparatus. This finding is disparate from previous observations that OPTN in cell types such as HeLa, 15,17 DU249 hepatoma, 16 dermal fibroblast, 10 and normal rat kidney 17 is localized to the Golgi. The disparity could reflect differences in cell types.…”

Section: Studies Of Optineurin a Glaucoma Gene 1985contrasting

confidence: 99%

“…10,[15][16][17] We performed immunofluorescence (Figure 2) and noted that in human TM and RPE cells, the endogenous OPTN (Figure 2 (Figure 2, A, c and f, and B, c and f). The lack of major colocalization was confirmed by confocal microscopy after sequential scanning.…”

Section: Localization Of Endogenous Optnmentioning

confidence: 99%

“…10,13 Previous studies suggested that OPTN might be associated with the Golgi apparatus. 10,[15][16][17] OPTN has been shown to interact with Rab8, huntingtin, and myosin VI. 14,17 Rab8 regulates membrane trafficking and is known to promote changes in cell shape by reorganizing actin and microtubules.…”

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confidence: 99%

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Studies of Optineurin, a Glaucoma Gene

Park

Shen

Samaraweera

et al. 2006

The American Journal of Pathology

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Optineurin (OPTN) has recently been linked to glaucoma, a major cause of blindness worldwide. Mutations in OPTN such as Glu 503 Lys (E50K) have been reported in patients, particularly those with normal pressure glaucoma. Here, we show that the endogenous OPTN was not secreted in two ocular cell types, human trabecular meshwork and retinal pigment epithelial cells. It localized instead in the cytoplasm in a diffuse pattern without a distinct association with the Golgi apparatus. When overexpressed, however, wild-type OPTN-green fluorescent protein (GFP) formed foci especially around the Golgi, colocalizing partially with the common endocytic pathway marker transferrin receptor in both cell types. Fragmentation of the Golgi was also observed. On nocodazole treatment, the OPTN foci were dispersed into the cytoplasm. Overexpression of mutant OPTN E50K -GFP resulted in a greater number (P < 0.0055) and size of the foci, compared with the wild type, and the Golgi alteration was potentiated. Cell loss observed in OPTN-expressing cultures was also more pronounced in OPTN E50K -GFP compared with that of wild-type OPTN-GFP counterparts (P < 0.01). This study highlights a possible role of OPTN in vesicle trafficking and Golgi integrity. It also provides insights into the possible mechanisms why E50K would exhibit a propensity toward the development of glaucoma.

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Section: Studies Of Optineurin a Glaucoma Gene 1985contrasting

confidence: 99%

Section: Localization Of Endogenous Optnmentioning

confidence: 99%

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Studies of Optineurin, a Glaucoma Gene

Park

Shen

Samaraweera

et al. 2006

The American Journal of Pathology

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“…Optineurin is a gene with unknown function, implicated in the development of primary open-angle glaucoma. 53 It contains significant sequence homology to IKKg, 54 and has been identified as a TNF-a-induced protein which is able to modulate TNF-amediated cell death. 55 Based on these observations, it has been speculated that optineurin could be a component of the TNF-a signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Activation of NF‐κB by extracellular S100A4: Analysis of signal transduction mechanisms and identification of target genes

Boye¹,

Grotterød

Aasheim

et al. 2008

Intl Journal of Cancer

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The metastasis-promoting protein S100A4 stimulates metastatic progression through both intracellular and extracellular functions. Extracellular activities of S100A4 include stimulation of angiogenesis, regulation of cell death and increased cell motility and invasion, but the exact molecular mechanisms by which extracellular S100A4 exerts these effects are incompletely elucidated. The aim of the present study was to characterize S100A4-induced signal transduction mechanisms and to identify S100A4 target genes. We demonstrate that extracellular S100A4 activates the transcription factor NF-jB in a subset of human cancer cell lines through induction of phosphorylation and subsequent degradation of the NF-jB inhibitor IjBa. Concomitantly, S100A4 induced a sustained activation of the MAP kinase JNK, whereas no increased activity of the MAP kinases p38 or ERK was observed. Microarray analyses identified 136 genes as being significantly regulated by S100A4 treatment, and potentially interesting S100A4-induced gene products include IjBa, p53, ephrin-A1 and optineurin. Increased expression of ephrin-A1 and optineurin was validated using RT-PCR, Western blotting and functional assays. Furthermore, S100A4-stimulated transcription of these target genes was dependent on activation of the NF-jB pathway. In conclusion, these findings contribute to the understanding of the complex molecular mechanisms responsible for the diverse biological functions of extracellular S100A4, and provide further evidence of how S100A4 may stimulate metastatic progression. ' 2008 Wiley-Liss, Inc.Key words: S100A4; NF-jB; MAP kinase; ephrin-A1The metastasis-promoting protein S100A4 is a member of the S100 family of small, Ca 21 -binding proteins. To date, 21 different S100 proteins have been identified and shown to be involved in a wide range of physiological functions.1,2 Several S100 family members have been implicated in tumor progression, and particularly S100A4 has been intimately linked to cancer metastasis. [3][4][5] Functional evidence of the direct involvement of S100A4 in the metastatic process was originally obtained from transfection studies, 6-8 and further substantiated by reports demonstrating increased metastasis formation in S100A4-transgenic mice crossed into a tumorigenic background. 9,10 Similar to certain other S100 proteins, S100A4 is also released to the extracellular space. Recently, extracellular S100A4 was demonstrated to increase the metastatic potential of S100A4-negative mouse mammary carcinoma cells, 11 and highly metastatic tumor cells were unable to form metastases in S100A4 knockout mice.12 These investigations strongly indicate that release of S100A4 from the tumor microenvironment is a crucial factor in the metastatic process. Additionally, extracellular S100A4 has been identified as a potent inducer of angiogenesis, 13,14 suggesting that tumor cell-derived S100A4 is also involved in tumor progression.The molecular mechanisms by which extracellular S100A4 promotes metastasis have not been extensively delineated, ...

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“…In unstimulated cells, Optn is localized at the Golgi apparatus and in vesicle-like structures, while overexpressed Optn is mostly detected in perinuclear structures called foci that are regulated by autophagy. 5,26,77 However, in different physiological or pathological conditions, Optn dissociates from the Golgi apparatus and accumulates at different subcellular locations.…”

Section: Subcellular Localization Of Optnmentioning

confidence: 99%