RAP80 binds p32 to preserve the functional integrity of mitochondria

Chung, Hee Jin; Korm, Sovannarith; Lee, Sein; Sophors, Phorl; Noh, Solhee; Han, Miae; Naskar, Rema; Kim, Hongtae; Lee, Joo‐Yong

doi:10.1016/j.bbrc.2017.08.077

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…also been associated with other cancer-related genes including BCR-ABL (Capala et al, 2016), the V600E-BRAF oncogene (Hall et al, 2013), and BRCA mutations (Chung et al, 2017;Henderson, 2012;Maniccia et al, 2009;Privat et al, 2014). Huang and colleagues showed that K-rasG12v transformation caused mitochondrial dysfunction and a metabolic switch from OxPhos to aerobic fermentation (Hu et al, 2012).…”

Section: Ll Open Accessmentioning

confidence: 99%

On the Origin of ATP Synthesis in Cancer

et al. 2020

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ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the DG 0 ATP hydrolysis of À56 kJ/mole is the endpoint of both genetic and metabolic processes required for life. Various anomalies in mitochondrial structure and function prevent maximal ATP synthesis through OxPhos in cancer cells. Little ATP synthesis would occur through glycolysis in cancer cells that express the dimeric form of pyruvate kinase M2. Mitochondrial substrate level phosphorylation (mSLP) in the glutamine-driven glutaminolysis pathway, substantiated by the succinate-CoA ligase reaction in the TCA cycle, can partially compensate for reduced ATP synthesis through both Ox-Phos and glycolysis. A protracted insufficiency of OxPhos coupled with elevated glycolysis and an auxiliary, fully operational mSLP, would cause a cell to enter its default state of unbridled proliferation with consequent dedifferentiation and apoptotic resistance, i.e., cancer. The simultaneous restriction of glucose and glutamine offers a therapeutic strategy for managing cancer.

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Section: Ll Open Accessmentioning

confidence: 99%

On the Origin of ATP Synthesis in Cancer

et al. 2020

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“…The negatively charged amino acid residues (mostly glutamate and aspartate) are mainly located on the soluble surface, while the membrane surface is mainly positively charged. This may explain how C1QBP binds to arginine-rich proteins, such as RAP80 containing an arginine-rich C-terminal domain or PR-DPR [49]. C1QBP can form homotrimers with a doughnut-like shape and the range of ligands for it is very broad [50][51][52][53].…”

Section: Discussionmentioning

confidence: 99%

“…C1QBP is also a chaperone protein for RNAs and proteins involved in mitochondrial translation and function. Notably, RAP80, a nuclear DNA damage repair protein, interacts with C1QBP in mitochondria, thereby mitochondrial protein biosynthesis [49]. Additionally, C1QBP can bind to components of the pyruvate dehydrogenase (PDH) complex located in the mitochondrial matrix, thereby regulating the synthesis of acetyl-CoA in the TCA cycle, and finally affecting ATP production.…”

Section: Discussionmentioning

confidence: 99%

C9-ALS-Associated Proline-Arginine Dipeptide Repeat Protein Induces Activation of NLRP3 Inflammasome of HMC3 Microglia Cells by Binding of Complement Component 1 Q Subcomponent-Binding Protein (C1QBP), and Syringin Prevents This Effect

Tsai

Chiu

et al. 2022

Cells

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Amyotrophic lateral sclerosis (ALS) is a fatal disease in which motor neurons gradually degenerate. The mutation of the C9orf72 gene is the main genetic cause of ALS (C9-ALS). One of its specific pathological features is the production of proline-arginine (PR) dipeptide repeat protein (DPR). In this study, we developed a PR-DPR (PR50)-expressing human HMC3 microglial cell model. We found that PR50 mainly aggregates into spots in the nucleus and induces significant NLRP3 inflammasome activity. Moreover, mouse NSC-34 motor neuron cells treated with a conditional medium of PR50-expressing HMC3 cells (PR-CM) caused cell damage and apoptosis activity. However, R50-expressing HMC cells treated with MCC950 (an NLRP3 inhibitor) reversed this result. Furthermore, we identified complement component 1 q subcomponent-binding protein (C1QBP) as one of the interaction partners of PR50. The downregulation of C1QBP in HMC3 cells induces NLRP3 inflammasome activity similar to PR50 expression. Finally, we found that syringin can block the interaction between PR50 and C1QBP, and effectively reduce the PR50-induced NLRP3 inflammasome activity in HMC3 cells. This improves the apoptosis of NSC-34 cells caused by PR-CM. This study is the first to link PR50, C1QBP, and NLRP3 inflammasome activity in microglia and develop potential therapeutic strategies for syringin intervention in C9-ALS.

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“…RAP80 is a member of BRCA1-A complex, which regulates the cell cycle checkpoint and DNA damage repair in the nucleus 1. DNA damage, mutations of tumor suppressor genes, and defects in DNA damage response (DDR) are critical events in carcinogenesis 2,3.…”

Section: Introductionmentioning

confidence: 99%

<p>RAP80 expression in breast cancer and its relationship with apoptosis in breast cancer cells</p>

Jin

Mao

Qiao

et al. 2019

OTT

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BackgroundRAP80 is a member of BRCA1-A complex, which plays an important role in regulating the cell cycle checkpoint and DNA damage repair in the nucleus.MethodWe investigated RAP80 expression in breast cancer and its paired normal breast tissues to further analyze its role in the biological behavior of breast cancer cells.ResultsRAP80 expression in breast cancer (62.3%, 101/162) was significantly lower than that in adjacent normal breast tissues (P<0.05). RAP80 expression was related to tumor size, lymph node metastasis, TNM stage, and molecular subtype (P<0.05). RAP80 mRNA expression was significantly lower in triple-negative breast cancer than other types. The mRNA and protein of RAP80 were obvious in MCF-7 and very weak in ZR-75 or MDA-MB-231, so we picked MCF-7 to be transfected with RAP80 siRNA. The survival rate of both cells decreased in a dose-dependent manner and the IC50 value for cisplatin in MCF-7 RAP80 siRNA cells was 0.83 µg/mL, and 1.69 µg/mL in wild-type MCF-7 according to MTT. RAP80 siRNA transfection upregulated the apoptosis and downregulated invasive or migrating ability of MCF-7. RAP80 siRNA also upregulated the protein expression of Caspase-3, cleaved Caspase-3, Apaf-1, Cytochrome C, Bax, and Fas, and downregulated the protein expression of Bcl-2.ConclusionRAP80 expression was related to ER or PR activity. Inhibition of RAP80 expression can induce apoptosis in breast cancer cells and improve chemosensitivity to cisplatin. Tumor cells can activate protective responses to inhibit cell cycle progression, which may be related to RAP80, and repair cisplatin-induced DNA damage. RAP80 is related to BRCA1’s effect, which can be used as an interesting target for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.

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RAP80 binds p32 to preserve the functional integrity of mitochondria

Cited by 5 publications

References 25 publications

On the Origin of ATP Synthesis in Cancer

On the Origin of ATP Synthesis in Cancer

C9-ALS-Associated Proline-Arginine Dipeptide Repeat Protein Induces Activation of NLRP3 Inflammasome of HMC3 Microglia Cells by Binding of Complement Component 1 Q Subcomponent-Binding Protein (C1QBP), and Syringin Prevents This Effect

<p>RAP80 expression in breast cancer and its relationship with apoptosis in breast cancer cells</p>

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