{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The collected studies reveal that “GPS1” can refer to distinct yet functionally related entities. In mammalian cells, GPS1 is the COP9 signalosome subunit 1 (also known as CSN1), where its N‐terminal domain exerts potent transcriptional repression – for example, by inhibiting c‐fos expression and AP-1 signaling (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In this context, mutations in GPS1 have been implicated in human cancer; recurrent mutations in GPS1 were shown to disrupt its proper subcellular localization (with AGO2 in cytoplasmic P‐bodies), thereby impairing microRNA-mediated gene silencing and contributing to penile cancer etiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, GPS1 functions as a critical regulator of intracellular signaling. One study demonstrated that the metabolic regulator Asb-4 interacts with GPS1 and downregulates its protein levels, which in turn reduces c-Jun N-terminal kinase (JNK) activity and the phosphorylation of insulin receptor substrate-1 – linking GPS1 to the modulation of stress and insulin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, GPS1 has been identified as an interacting partner of intraflagellar transport proteins in T cells where it is incorporated into a complex that facilitates the coordinated trafficking of receptors to the immune synapse, thereby affecting downstream signaling events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In a related study in influenza virus–infected cells, downregulation of GPS1 was found to impair viral polymerase activity via effects on NF-κB signaling, underscoring its role in regulating infection‐related transcriptional responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n GPS1’s functional roles extend beyond mammals. In plant systems, “GPS1” denotes a FRET-based biosensor (Gibberellin Perception Sensor 1) that enables in vivo mapping of cellular gibberellin gradients, thereby providing insight into hormone-regulated growth processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, in the context of abscisic acid (ABA) signaling, a study identified GPS1 (as part of the COP9 signalosome) as a binding partner of the ABA receptor PYL5, suggesting that it may participate in the crosstalk between hormonal regulation and protein degradation pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in invertebrates such as shrimp, GPS1 (CSN1) has been shown to interact with the Notch receptor. This interaction appears to downregulate NF-κB pathway activity, indicating a role for GPS1 in modulating immune responses in these organisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the multifaceted functions of GPS1/CSN1 span transcriptional repression, modulation of kinase and NF-κB signaling, and the regulation of receptor trafficking in mammalian immune cells, while in plants it serves as a biosensor for gibberellin and a component of ABA signaling. Collectively, these studies underscore the importance of GPS1 as an integrative regulator in diverse cellular contexts across different organisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Tsuge, M Matsui, N Wei "}, {"type": "b", "children": [{"type": "t", "text": "The subunit 1 of the COP9 signalosome suppresses gene expression through its N-terminal domain and incorporates into the complex through the PCI domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/jmbi.2000.4288"}], "href": "https://doi.org/10.1006/jmbi.2000.4288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11114242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11114242"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrew Feber, Daniel C Worth, Ankur Chakravarthy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-15-3134"}], "href": "https://doi.org/10.1158/0008-5472.CAN-15-3134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27325650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27325650"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ji-Yao Li, Biao-Xin Chai, Weizhen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ankyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2006.12.010"}], "href": "https://doi.org/10.1016/j.cellsig.2006.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17276034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17276034"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Donatella Galgano, Anna Onnis, Elisa Pappalardo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The T cell IFT20 interactome reveals new players in immune synapse assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.200006"}], "href": "https://doi.org/10.1242/jcs.200006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28154159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28154159"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tomoko Kuwahara, Seiya Yamayoshi, Takeshi Noda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mBio (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mBio.02867-19"}], "href": "https://doi.org/10.1128/mBio.02867-19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31848286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31848286"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Annalisa Rizza, Ankit Walia, Bijun Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Visualizing Cellular Gibberellin Levels Using the nlsGPS1 Förster Resonance Energy Transfer (FRET) Biosensor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Vis Exp (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3791/58739"}], "href": "https://doi.org/10.3791/58739"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30688303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30688303"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qizhen Zheng, Liang Zhang, Qian Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of Interacting Proteins of ABA Receptor PYL5 "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "via"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Covalent Chemical Capture."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Chem Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acschembio.9b00806"}], "href": "https://doi.org/10.1021/acschembio.9b00806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31617999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31617999"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Weiling Zhao, Zhihong Zheng, Jude Juventus Aweya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Litopenaeus vannamei Notch interacts with COP9 signalosome complex subunit 1 (CNS1) to negatively regulate the NF-κB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteomics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jprot.2020.104074"}], "href": "https://doi.org/10.1016/j.jprot.2020.104074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33309928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33309928"}]}]}]}