Interaction of the taxilin family with the nascent polypeptide‐associated complex that is involved in the transcriptional and translational processes

Yoshida, Kenji; Nogami, Satoru; Satoh, Sachie; Tanaka-Nakadate, Sawako; Hiraishi, Hideyuki; Terano, Akira; Shirataki, Hiromichi

doi:10.1111/j.1365-2443.2005.00848.x

Cited by 28 publications

(41 citation statements)

References 25 publications

(52 reference statements)

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“…37 Furthermore, aNAC was reported to interact with g-taxilin, which inhibits ATF4-mediated transcription. 18,19 In this study, we showed that aNAC ablation by the RNA interference resulted in the upregulation of ATF4 and downregulation of g-taxilin (Figure 4a), consistent with the previous findings. Therefore, these studies imply that aNAC and eIF2a might coordinately regulate transcriptional and translational responses of the cell to hypoxia, thereby determining the fate of the hypoxic cell.…”

Section: Discussionsupporting

confidence: 80%

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αNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia

Hotokezaka

Leyen

et al. 2009

Cell Death Differ

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Accumulation of unfolded proteins triggers endoplasmic reticulum (ER) stress and is considered a part of the cellular responses to hypoxia. The nascent polypeptide-associated complex (NAC) participates in the proper maturation of newly synthesized proteins. However, thus far, there have been no comprehensive studies on NAC involvement in hypoxic stress. Here, we show that hypoxia activates glycogen synthase kinase-3b (GSK-3b) and that the activated GSK-3b destabilizes aNAC with the subsequent apoptosis of the cell. Hypoxia of various cell types and the mouse ischemic brain was associated with rapid downregulation of aNAC and ER stress responses involving PERK, ATF4, c-taxilin, elF2a, Bip, and CHOP. Depletion of aNAC by RNA interference specifically activated ER stress responses and caused mitochondrial dysfunction, which resulted in apoptosis through caspase activation. Interestingly, we found that the hypoxic conditions activated GSK-3b, and that GSK-3b inhibition prevented aNAC protein downregulation in hypoxic cells and rescued the cells from apoptosis. In addition, aNAC overexpression increased the viability of hypoxic cells. Taken together, these results suggest that aNAC degradation triggers ER stress responses and initiates apoptotic processes in hypoxic cells, and that GSK-3b may participate upstream in this mechanism.

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Section: Discussionsupporting

confidence: 80%

“…Previous reports have shown that g-taxilin is a regulator of ATF4 activity and interacts with aNAC. 18,19 Therefore, we assessed g-taxilin protein Figure S2).…”

Section: Resultsmentioning

confidence: 99%

αNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia

Hotokezaka

Leyen

et al. 2009

Cell Death Differ

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“…Therefore, these findings suggest that the taxilin family could play an important role in the process of translation through interaction with NAC, as well as transcription through interaction with αNAC alone (44). Correct transmission of genetic information through both transcriptional and translational processes is important for normal cell function.…”

Section: Referencesmentioning

confidence: 99%

“…On the other hand, it has been recently reported that α-taxilin interacts with the nascent polypeptide-associated complex (NAC), mainly through its alphasubunit (αNAC) (44). There is increasing evidence binding protein involved in intracellular vesicle trafficking (26).…”

Section: Transcription and Translationmentioning

confidence: 99%

Increased alpha-taxilin protein expression is associated with the metastatic and invasive potential of renal cell cancer

et al. 2011

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Intracellular vesicle trafficking is the principal transportation system in eukaryotic cells, and is considered to be involved in a variety of processes related to cell proliferation. A protein named alpha-taxilin has been identified as a binding partner of the syntaxin family, which coordinates intracellular vesicle trafficking. To clarify the role of alpha-taxilin in renal cell carcinoma (RCC), we investigated alpha-taxilin protein expression in clear cell RCC tissues. We analyzed alphataxilin protein in matched sets of tumor and non-tumor tissues from the surgical specimens of 52 Japanese RCC patients by Western blotting. We also studied the relation between alpha-taxilin protein expression in tumor tissues and various clinicopathological features. The alpha-taxilin protein level was higher in tumor tissues than in non-tumor tissues (P < 0.05). Increased expression of alpha-taxilin protein in primary tumors was related to local invasion (P < 0.001), pathological vessel invasion (P < 0.001), and metastasis (P < 0.0001). Kaplan-Meier plots of survival for patients with low versus high alpha-taxilin expression revealed that high expression in tumor tissues was associated with shorter overall survival in all patients (P < 0.05) and with shorter disease-free survival in patients without metastasis (P < 0.01). These findings suggest that alpha-taxilin influences the metastatic and invasive potential of RCC.Intracellular vesicle trafficking is the principal transportation system in eukaryotic cells, and vesicle trafficking is thought to be involved in various processes related to cell proliferation. Abnormal proliferation is the hallmark of cancer. Recently, a protein named alpha (α)-taxilin was identified as a binding partner of the syntaxin family, which is involved in the coordination of intracellular vesicle trafficking (26). The taxilin family has at least three members-α-, beta (β)-, and gamma (γ)-taxilin-and α-taxilin possesses an extremely long coiled-coil region and interacts with syntaxin family members localized on the plasma membrane, but not with those localized on intracellular organelles (26, 28). There is evidence that the taxilin family is involved in the transfer of vesicles delivered to the plasma membrane (26, 28). However, the precise influence of the taxilin family on the functions of the syntaxin family remains to be fully elucidated, and the actual role of α-taxilin in intracellular vesicle trafficking is also unknown. In addition to providing information about the molecular mechanisms involved, examination of the physiological and pathophysiological functions of taxilin should improve our understanding about the role of this family of proteins. We recently reported that α-taxilin protein is significantly upregulated in proliferating neural stem cells during embryonic development in the rat (37). In addition, Oba-Shinjo et al. recently reported that

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“…The polyclonal anti-human ·-taxilin antibody raised in a rabbit was used for immunohistochemistry, as previously described (12).…”

Section: Methodsmentioning

confidence: 99%

Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor

Tomiya¹

2010

Int J Oncol

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Abstract. The membrane traffic system has been recognized to be involved in carcinogenesis and tumor progression in several types of tumors. ·-taxilin is a newly identified membrane traffic-related molecule, and its up-regulation has been reported in embryonic and malignant tissues of neural origin. In the present study, we analyzed the expression of ·-taxilin in relation to clinicopathological features of hepatocellular carcinomas (HCC) and proliferative activity of the tumor determined by proliferating cell nuclear antigen labeling index (PCNA-LI). Twenty-nine surgically resected nodules of HCC (8 well-, 11 moderately-, and 10 poorlydifferentiated) were studied. Fifteen cases showed 'strong staining', while 14 cases showed 'weak staining' for ·-taxilin. A significantly higher expression of ·-taxilin was observed in less-differentiated (p=0.005), and more invasive (p=0.016) HCCs. The 'strong staining' group showed significantly higher PCNA-LI than the 'weak staining' group (the medians of PCNA-LI were 59.4% vs. 14.4%, p<0.0001). We also evaluated the expression of ·-taxilin in hepatoma cell lines (PLC/PRF/5, Hep G2 and HuH-6) in association with cell proliferation. The expression levels of ·-taxilin protein were correlated with their growth rates. In conclusion, the expression of the ·-taxilin protein was related with an increased proliferative activity and a less-differentiated histological grade of HCC. ·-taxilin may be involved in cell proliferation of HCC, and its expression can be a marker of malignant potential of HCC.

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Interaction of the taxilin family with the nascent polypeptide‐associated complex that is involved in the transcriptional and translational processes

Cited by 28 publications

References 25 publications

αNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia

αNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia

Increased alpha-taxilin protein expression is associated with the metastatic and invasive potential of renal cell cancer

Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor

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