The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance

Tang, Ruijun; Jiang, Z. Gordon; Chen, Fang; Yu, Weiyu; Fan, Kaijing; Tan, Jieqiong; Zhang, Zhuohua; Liu, Xing; Li, Pishun; Yuan, Kai

doi:10.1016/j.celrep.2020.107794

Cited by 11 publications

(14 citation statements)

References 77 publications

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“…This is perhaps due to the essentiality of mitotic genes for the life of a cell, especially when being cultured in a petri dish. Nonetheless, mitotic genes are often expressed in postmitotic tissues, and several recent studies in model organisms including mice and Drosophila have revealed unexpected roles of mitotic regulators in endocytosis [87][88][89].…”

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

“…Studies in Drosophila have further consolidated this model and suggest it might be an evolutionarily conserved mechanism (Fig. 5B) [89]. The kinase domain of Drosophila BubR1 is able to interact with Drosophila AP2B, and a MIM‐like motif can also be identified on the cytoplasmic tail of Drosophila InR, although this cytoplasmic tail is not very conserved at sequence level between Drosophila and mice.…”

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

“…Drosophila BubR1 however still has an intact kinase domain and it is functional [101]. Interestingly, introduction of point mutations to inactivate the Drosophila BubR1 kinase leads to a series of phenotypic changes that are associated with attenuated insulin signaling [89]. The InR on the plasma membrane is reduced, and the PI3K signaling pathway becomes less activated.…”

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

“…The InR on the plasma membrane is reduced, and the PI3K signaling pathway becomes less activated. These mutations in the kinase domain do not interfere or weaken the interaction with AP2B, suggesting that the kinase activity of BubR1 itself is involved in regulating the clathrin‐mediated endocytosis of InR in Drosophila [89]. This regulatory role might be lost or compensated by other kinases, as BubR1 degenerates its kinase domain in evolution.…”

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

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Functional reciprocity of proteins involved in mitosis and endocytosis

et al. 2020

The FEBS Journal

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Mitosis and endocytosis are two fundamental cellular processes essential for maintaining a eukaryotic life. Mitosis partitions duplicated chromatin enveloped in the nuclear membrane into two new cells, whereas endocytosis takes in extracellular substances through membrane invagination. These two processes are spatiotemporally separated and seemingly unrelated. However, recent studies have uncovered that endocytic proteins have moonlighting functions in mitosis, and mitotic complexes manifest additional roles in endocytosis. In this review, we summarize important proteins or protein complexes that participate in both processes, compare their mechanism of action, and discuss the rationale behind this multifunctionality. We also speculate on the possible origin of the functional reciprocity from an evolutionary perspective. An introduction to mitosis and endocytic pathwaysEukaryotic cells rely on endocytosis to uptake extracellular materials and their own plasma membrane components, in order to maintain homeostasis and respond to the varying environment [1-3]; they use the process of mitosis to achieve self-duplication and cell fate specification when differentiating [1,4]. These two Abbreviations AP2, adaptor protein-2; APC/C, anaphase-promoting complex/cyclosome; CCP, clathrin-coated pit; CCV, clathrin-coated vesicle; CHC, clathrin heavy chains; ch-TOG, colonic and hepatic tumor overexpressed gene; CLC, clathrin light chain; CME, clathrin-mediated endocytosis; CPC, chromosome passenger complex;

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Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

Section: Functional Engagement Of Mitotic Regulators In Endocytosismentioning

confidence: 99%

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Functional reciprocity of proteins involved in mitosis and endocytosis

et al. 2020

The FEBS Journal

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“…Insulin promotes clathrin-mediated IR endocytosis, which controls the intensity and duration of insulin signaling (50,(56)(57)(58). We and others have previously shown that mitotic regulators and SHP2 (SH2-containing protein tyrosine phosphatase 2)-MAPK (mitogen-activated protein kinase) pathway promote insulin-induced IR endocytosis (59)(60)(61). To study the contributions of the disulfide-linked αCTs to IR endocytosis, we generated HeLa cells stably expressing IR-GFP-WT, -3CS, or -D686-690, and examined the subcellular localization of these IR-GFP proteins (Fig.…”

Section: The Disulfide-linked αCts Are Required For Optimal Ir Signal...mentioning

confidence: 99%

Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor

Bai

et al. 2022

Preprint

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The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked homodimers in the apo-state; however, their ligand binding properties and the structures in the active state differ substantially. It has been proposed that the disulfide-linked C-terminal segment of α-chain (αCTs) of the IR and IGF1R control the cooperativity of ligand binding and regulate the receptor activation. Nevertheless, the molecular basis for the roles of disulfide-linked αCTs in IR and IGF1R activation are still unclear. Here, we report the cryo-EM structures of full-length mouse IGF1R/IGF1 and IR/insulin complexes with modified αCTs that have increased flexibility. Unlike the Γ-shaped asymmetric IGF1R dimer with a single IGF1 bound, the IGF1R with the enhanced flexibility of αCTs can form a T-shaped symmetric dimer with two IGF1s bound. Meanwhile, the IR with non-covalently linked αCTs predominantly adopts an asymmetric conformation with four insulins bound, which is distinct from the T-shaped symmetric IR. Using cell-based experiments, we further showed that both IGF1R and IR with the modified αCTs cannot activate the downstream signaling potently. Collectively, our studies demonstrate that the certain structural rigidity of disulfide-linked αCTs is critical for optimal IR and IGF1R signaling activation.

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GSE1 promotes the proliferation and migration of lung adenocarcinoma cells by downregulating KLF6 expression

Meng,

Yang,

et al. 2024

Cell Biology International

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Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF–HDAC complex (BHC) components in cells. The transcriptome of GSE1‐knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p‐value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel‐like factor 6). Indeed, quantitative reverse‐transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non‐small cell lung cancer cells through the downregulation of KLF6 expression.

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The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance

Abstract: Highlights d BubR1 kinase activity is dispensable for the timing and progression of mitosis d BubR1 kinase-dead mutants have attenuated insulin signaling d Loss of BubR1 kinase activity compromises the homeostasis of tissue stem cells

Cited by 11 publications

References 77 publications

Functional reciprocity of proteins involved in mitosis and endocytosis

Functional reciprocity of proteins involved in mitosis and endocytosis

Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor

GSE1 promotes the proliferation and migration of lung adenocarcinoma cells by downregulating KLF6 expression

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