Centaurin-α1 associates in vitro and in vivo with nucleolin

Dubois, Thierry; Zemlickova, Eva; Howell, Steven; Aitken, Alastair

doi:10.1016/s0006-291x(02)03010-3

Cited by 27 publications

(16 citation statements)

References 21 publications

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“…ARF guanine-nucleotide exchange factors such as BRAG2 have been detected in nuclei both biochemically and morphologically (Dunphy et al, 2007). Moreover, both BIG1, a guanine-nucleotide exchange factor that is localized to the trans-Golgi network at steady state, and Centaurin a1, a GTPase-activating protein for ARF6, have been reported to enter the nucleus and interact with the nucleolar protein nucleolin (Dubois et al, 2003;Padilla et al, 2008). Similarly, PIKE (AGAP2/Centaurin-g1) was also found within nuclei (Dunphy et al, 2007).…”

Section: Discussionmentioning

confidence: 98%

ARF1 controls proliferation of breast cancer cells by regulating the retinoblastoma protein

et al. 2011

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The ADP-ribosylation factors (ARFs) 1 and 6 are small GTP-binding proteins, highly expressed and activated in several breast cancer cell lines and are associated with enhanced migration and invasiveness. In this study, we report that ARF1 has a critical role in cell proliferation. Depletion of this GTPase or expression of a dominant negative form, which both resulted in diminished ARF1 activity, led to sustained cell-growth arrest. This cellular response was associated with the induction of senescent markers in highly invasive breast cancer cells as well as in control mammary epithelial cells by a mechanism regulating retinoblastoma protein (pRB) function. When examining the role of ARF1, we found that this GTPase was highly activated in normal proliferative conditions, and that a limited amount could be found in the nucleus, associated with the chromatin of MDA-MB-231 cells. However, when cells were arrested in the G 0 /G 1 phase or transfected with a dominant negative form of ARF1, the total level of activated ARF1 was markedly reduced and the GTPase significantly enriched in the chromatin. Using biochemical approaches, we demonstrated that the GDP-bound form of ARF1 directly interacted with pRB, but not other members of this family of proteins. In addition, depletion of ARF1 or expression of ARF1T 31 N resulted in the constitutive association of pRB and E2F1, thereby stabilizing the interaction of E2F1 as well as pRB at endogenous sites of target gene promoters, preventing expression of E2F target genes, such as cyclin D1, Mcm6 and E2F1, important for cell-cycle progression. These novel findings provide direct physiological and molecular evidence for the role of ARF1 in controlling cell proliferation, dependent on its ability to regulate pRB/E2F1 activity and gene expression for enhanced proliferation and breast cancer progression.

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Section: Discussionmentioning

confidence: 98%

ARF1 controls proliferation of breast cancer cells by regulating the retinoblastoma protein

et al. 2011

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“…The reasons for further analysis of nucleolin in the current study are several; including 1) although unreported in PD, levels of nucleolin appear to be altered in Alzheimer disease (AD), Down Syndrome (DS) and progressive supranuclear palsy (PSP) [6, 7, 13, 23]; 2) studies have demonstrated an involvement of nucleolin in the posttranscriptional regulation of amyloid precursor protein (APP) mRNA, a key protein associated with AD pathogenesis [27-29]; and 3) nucleolin, a protein observed within the nucleus, cytoplasm, as well as on the plasma membrane [6, 12, 16], appears to be involved in several aspects of cellular homeostasis, including cell proliferation, ribosomal biogenesis, signal transduction, chaperone/shuttling of cellular components, and apoptosis [4, 5, 8, 11, 12, 22]. …”

Section: Introductionmentioning

confidence: 99%

A role for a novel protein, nucleolin, in Parkinson's disease

Caudle

Kitsou

et al. 2009

Neuroscience Letters

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Although much has been learned in the last few decades concerning the molecular mechanisms and pathways associated with the development of familial as well as sporadic Parkinson disease (PD), the precise mechanisms and specific proteins responsible for mediating these effects remain to be elucidated. Thus, the identification and biological evaluation of novel proteins involved in these pathways is critical to providing a more comprehensive understanding of PD pathogenesis. Previously, in a cellular model of PD, we identified nucleolin as a protein interacting with α-synuclein and DJ-1, two critical proteins involved in PD pathogenesis. In our current study, we found the expression levels of nucleolin were dramatically reduced in the substantia nigra pars compacta of human PD subjects, compared with controls. Furthermore, manipulation of nucleolin in an in vitro model of PD resulted in significant alterations in generation of oxidative stress as well as proteasomal inhibition following rotenone exposure. Interestingly, nucleolin expression did not influence mitochondrial complex I activity, suggesting a selective specificity for oxidative stress and proteasomal pathways.

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“…17 in addition, aDaP1 interacts with casein kinase i and nucleolin, suggesting that the upregulated aDaP1 in aD neurons may serve as a docking protein to recruit signaling molecules such as different subtypes of casein kinase i to the plasma membrane. 18,19 This functional interaction of aDaP1 in possible neuronal damage may make it an appropriate target for preventing neurodegenerative processes. 20 finally, agaP1 (arfgaP with gTPase domain, ankyrin repeat, and PH domain 1) has been regarded as an autism susceptibility gene.…”

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confidence: 99%

High-Throughput Fluorescence Polarization Assay for the Enzymatic Activity of GTPase-Activating Protein of ADP-Ribosylation Factor (ARFGAP)

et al. 2011

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GTPase-activating proteins of ADP-ribosylation factors (ARFGAPs) play key cellular roles in vesicle production and trafficking, adhesion, migration, and development. Dysfunctional regulation of ARFGAPs has been implicated in various diseases, including cancer, Alzheimer disease, and autism. Unfortunately, there are few mechanistic details describing how ARFGAPs contribute to disease states. In this regard, it would be extremely helpful to have a set of small molecules that selectively and directly modulate specific ARFGAPs as probes to dissect ARFGAP-regulated cell signaling under various conditions. Currently, such probes are lacking, and their identification is hampered by the lack of a suitable high-throughput assay to monitor ARFGAP activity. Here, the authors describe and validate a robust high-throughput assay using fluorescence polarization to monitor the ability of diverse ARFGAPs to enhance the capacity of ARF1 to hydrolyze guanosine triphosphate.

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Centaurin-α1 associates in vitro and in vivo with nucleolin

Cited by 27 publications

References 21 publications

ARF1 controls proliferation of breast cancer cells by regulating the retinoblastoma protein

ARF1 controls proliferation of breast cancer cells by regulating the retinoblastoma protein

A role for a novel protein, nucleolin, in Parkinson's disease

High-Throughput Fluorescence Polarization Assay for the Enzymatic Activity of GTPase-Activating Protein of ADP-Ribosylation Factor (ARFGAP)

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