Dataset Information

Interaction of Arl1-GTP with GRIP domains recruits autoantigens Golgin-97 and Golgin-245/p230 onto the Golgi.

ABSTRACT: A cellular role and the mechanism of action for small GTPase Arl1 have been defined. Arl1-GTP interacts with the GRIP domains of Golgin-97 and Golgin-245, a process dependent on conserved residues of the GRIP domains that are important for Golgi targeting. The switch II region of Arl1 confers the specificity of this interaction. Arl1-GTP mediates Golgi recruitment of Golgin-97 in a switch II-dependent manner, whereas tethering Arl1-GTP onto endosomes can mediate endosomal targeting of Golgin-97. Golgin-97 and Golgin-245 are dissociated from the Golgi when Arl1 is knocked-down by its siRNA. Arl1-GTP thus functions to recruit Golgin-97 and Golgin-245 onto the Golgi via interacting with their GRIP domains.

SUBMITTER: Lu L

PROVIDER: S-EPMC196566 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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Interaction of Arl1-GTP with GRIP domains recruits autoantigens Golgin-97 and Golgin-245/p230 onto the Golgi.

Lu Lei L Hong Wanjin W

Molecular biology of the cell 20030518 9

A cellular role and the mechanism of action for small GTPase Arl1 have been defined. Arl1-GTP interacts with the GRIP domains of Golgin-97 and Golgin-245, a process dependent on conserved residues of the GRIP domains that are important for Golgi targeting. The switch II region of Arl1 confers the specificity of this interaction. Arl1-GTP mediates Golgi recruitment of Golgin-97 in a switch II-dependent manner, whereas tethering Arl1-GTP onto endosomes can mediate endosomal targeting of Golgin-97. ...[more]

PMID: 12972563

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Project description:BackgroundGolgin-97 is a tethering factor in the trans-Golgi network (TGN) and is crucial for vesicular trafficking and maintaining cell polarity. However, the significance of golgin-97 in human diseases such as cancer remains unclear.MethodsWe searched for a potential role of golgin-97 in cancers using Kaplan-Meier Plotter ( http://kmplot.com ) and Oncomine ( www.oncomine.org ) datasets. Specific functions of golgin-97 in migration and invasion were examined in golgin-97-knockdown and golgin-97-overexpressing cells. cDNA microarray, pathway analysis and qPCR were used to identify gene profiles regulated by golgin-97. The role of golgin-97 in NF-?B signaling pathway was examined by using subcellular fractionation, luciferase reporter assay, western blot analysis and immunofluorescence assay (IFA).ResultsWe found that low expression of golgin-97 correlated with poor overall survival of cancer patients and was associated with invasiveness in breast cancer cells. Golgin-97 knockdown promoted cell migration and invasion, whereas re-expression of golgin-97 restored the above phenotypes in breast cancer cells. Microarray and pathway analyses revealed that golgin-97 knockdown induced the expression of several invasion-promoting genes that were transcriptionally regulated by NF-?B p65. Mechanistically, golgin-97 knockdown significantly reduced I?B? protein levels and activated NF-?B, whereas neither I?B? levels nor NF-?B activity was changed in TGN46- or GCC185-knockdown cells. Conversely, golgin-97 overexpression suppressed NF-?B activity and restored the levels of I?B? in golgin-97-knockdown cells. Interestingly, the results of Golgi-disturbing agent treatment revealed that the loss of Golgi integrity was not involved in the NF-?B activation induced by golgin-97 knockdown. Moreover, both TGN-bound and cytosolic golgin-97 inhibited NF-?B activation, indicating that golgin-97 functions as an NF-?B suppressor regardless of its subcellular localization.ConclusionOur results collectively demonstrate a novel and suppressive role of golgin-97 in cancer invasiveness. We also provide a new avenue for exploring the relationship between the TGN, golgin-97 and NF-?B signaling in tumor progression.

Dataset Information

Interaction of Arl1-GTP with GRIP domains recruits autoantigens Golgin-97 and Golgin-245/p230 onto the Golgi.

Publications

Interaction of Arl1-GTP with GRIP domains recruits autoantigens Golgin-97 and Golgin-245/p230 onto the Golgi.

Similar Datasets

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