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1.
Phys Chem Chem Phys ; 26(19): 14131-14139, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690682

RESUMO

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.


Assuntos
Compostos de Bário , Micro-Ondas , Espécies Reativas de Oxigênio , Titânio , Titânio/química , Compostos de Bário/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Neoplasias , Catálise , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
2.
Opt Express ; 31(21): 34470-34476, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859202

RESUMO

Realization of nonreciprocal transport is of great importance in the development of devices and systems that require the directional manipulation of signals or particles in information processing and modern physics. For ultracold atomic systems, the approaches based on synthetic dimensions have led to rapid advances in engineering quantum transport. Here, we use laser-coupled discrete momentum states of noninteracting ultracold atoms to synthesize a momentum lattice, and construct a closed ring with controllable tunneling phase in the momentum lattice. We measure the density evolution of atoms in the synthetic lattice with the single-site resolution, and observe the nonreciprocal dynamics by controlling the tunneling phase. We show the effect of both the applied phase and the coupling strength between two distinct population regions on the population distribution of atoms in the momentum lattice, and provide the optimal parameters for achieving the nonreciprocal transport.

3.
Inflamm Res ; 71(10-11): 1213-1227, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35802146

RESUMO

BACKGROUND: Acute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored. METHODS: Acute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay. RESULTS: Caffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78. CONCLUSION: Caffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.


Assuntos
Cafeína , Doença Hepática Induzida por Substâncias e Drogas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Ubiquitina-Proteína Ligases Nedd4 , Animais , Camundongos , Apoptose , Cafeína/farmacologia , Cafeína/uso terapêutico , Chaperona BiP do Retículo Endoplasmático/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Ubiquitinação , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico
4.
Phys Chem Chem Phys ; 24(24): 15135-15139, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35699449

RESUMO

We report the high-resolution photoassociation (PA) spectroscopy of 23Na excited from the spin-1 Bose-Einstein Condensate (BEC) to the molecular state of 0g-(P3/2)v = 4 and 1g(P3/2)v = 91. By comparing the PA spectra of different spin configurations, we experimentally studied the effect of spin on the PA spectra. The experimental spectra comply well with the theoretical consideration. The results will play an important role in the study of the spin interaction and control of the antiferromagnetism in Na.

5.
Molecules ; 27(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36144778

RESUMO

A series of exohedral actinide borospherenes, An&Bm, and endohedral borospherenes, An@Bn (An=U, Np, Pu; m = 28, 32, 34, 36, 38, 40; n = 36, 38, 40), have been characterized by density functional theory calculations. The electronic structures, chemical bond topological properties and spectra have been systematically investigated. It was found that An@Bn is more stable than An&Bn in terms of structure and energy, and UB36 in an aqueous solution is the most stable molecular in this research. The IR and UV-vis spectra of An&Bm and An@Bn are computationally predicted to facilitate further experimental investigations. Charge-transfer spectroscopy decomposes the total UV-Vis absorption curve into the contributions of different excitation features, allowing insight into what form of electronic excitation the UV-Vis absorption peak is from the perspective of charge transfer between the An atoms and borospherenes.

6.
Opt Express ; 29(21): 32892-32899, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809111

RESUMO

Herein, we report on the experimental observations and a quantitative determination of the laser-induced frequency shift (LIFS) in the photoassociation (PA) spectra of spinor Bose-Einstein condensate of sodium. Our investigations revealed a nonlinear dependence of the LIFS on the intensity of PA laser. By developing a model within the quadratic Stark effect, we simulate the experimental results via a theoretical model that confirms the former. The experimental observations and the theoretical analysis can further improve the accuracy of investigations on important molecular properties and on preparation of specific molecular states, with possible applications in various key fields.

7.
Appl Opt ; 60(13): 3849-3855, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33983322

RESUMO

We propose a twisted microfiber interferometer sensor coated with boron nitride (BN) nanosheets for simultaneous measurement of relative humidity (RH) and temperature ($ T $). Sensitive material characteristics (BN nanosheets) enhance refractive index (RI) sensing sensitivity of proposed devices. A twisting process on the microfiber surely improves the evanescent field interaction with the deposited layer. The experimental results show that the RH sensitivities are ${-}{121.6}\;{\rm pm}/\% {\rm RH}$ and 0.26 dBm/%RH for humidity range from 46% to 72% and $ T $ sensitivities of 23.5 pm/°C and ${-}{0.045}\;{\rm dBm}/^\circ {\rm C}$ from 50°C to 90°C. The twisted microfiber interferometer has the advantages of compact structure, high sensitivity, and multiparameter measurement, which has certain potential for more applications.

8.
Phys Chem Chem Phys ; 22(7): 3809-3816, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31872827

RESUMO

We report new observations of the hyperfine structure in three ro-vibrational levels of the b3Π2 state of NaCs near the dissociation limit 3S1/2 + 6P3/2. The experiment was done via photoassociation of ultracold atoms in a dual-species dark-spot magneto-optical trap, and the spectra were measured as atomic trap losses. The simulation of the hyperfine structure showed that the greater part of the observed structure belongs to almost isolated levels of the b3Π2 state, but there are other parts of mixed character where the contribution from the 1Σ symmetry dominates.

9.
Appl Opt ; 59(36): 11261-11265, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33362048

RESUMO

The microfiber-optic interferential sensor based on polyaniline (PANI) sensing layer is efficiently performed in pH detection. The refractive index changes of PANI film can be translated into a significant wavelength shift in the interferometric fringe. We demonstrate the feasibility of PANI attached to the fiber surface in studying the interface polymerization method. The sensing performances of an improved sensitivity in acid solution with -0.54nm/pH and alkaline solution with 0.28 nm/pH are systematically investigated. By taking advantage of its miniature size and mechanical flexibility, the microfiber interferential sensor might make a promising platform for pH measurement.

10.
Fish Shellfish Immunol ; 89: 18-26, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30905838

RESUMO

Triploid hybrid (3n = 150) of red crucian carp (♀, 2n = 100) and allotetraploid (♂, 4n = 200) presents the obviously stronger disease resistance than its parents. To elucidate the innate immunity of triploid hybrid, the MAVS homologues of triploid hybrid (3nMAVS), red crucian carp (2nMAVS) and allotetraploid (4nMAVS) have been identified and characterized separately in this study. 2nMAVS and 4nMAVS were evolutionarily conserved; however, 3nMAVS showed lower amino acid similarity and differently predicted structure to 2nMAVS or 4nMAVS. 3nMAVS transcription increase rate in host cells were obviously higher than 2nMAVS or 4nMAVS in response to different stimuli, which included spring viraemia of carp virus (SVCV), grass carp reovirus (GCRV) and poly (I:C). The reporter assay in EPC cells showed that 3nMAVS owned much stronger ability to induce the production of DrIFNφ1 and eIFN than either 2nMAVS or 4nMAVS. Accordingly, EPC cells transfected with 3nMAVS presented obviously stronger antiviral activity against both GCRV and SVCV than the cells expressing 2nMAVS or 4nMAVS. All the data support the conclusion that 3nMAVS-mediated antiviral signaling during innate immune activation was stronger than those of 2nMAVS and 4nMAVS, which provided us the new insight on the innate immune system of triploid hybrid.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Carpas/genética , Carpas/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunidade Inata/genética , Animais , Cruzamento , Doenças dos Peixes/imunologia , Poli I-C/farmacologia , Reoviridae/fisiologia , Infecções por Reoviridae/imunologia , Infecções por Reoviridae/veterinária , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Tetraploidia , Triploidia
11.
Nanotechnology ; 29(40): 405504, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30015628

RESUMO

Self-powered wearable sensing-textiles for real-time detecting environmental atmosphere and body motion have been presented. The textile is based on highly-stretchable conductive ecoflex fiber modified with multiwall carbon nanotube and polyaniline (PANI) derivatives (acting as one electrode). The surface of the fiber is twined with varnished wire (acting as the other electrode). Upon applied deformation of stretching or bending, the sensing-textile can harvest the mechanical energy and output electric signals through the triboelectrification effect between PANI and varnished wire. After being attached on the human body, the triboelectric output of the sensing-textile can be used to monitor body motion, including finger bending and body stretching. Interestingly, the triboelectric output of the sensing-textile is significantly dependent on the atmosphere, which can actively distinguish different gas species in the environment. The sensitivity, stability and selectivity against ethanol, ammonia, acetone and formaldehyde are high. The response against 400 ppm ethanol vapor at room temperature is up to 54.73%. The current density is 2.1 × 10-4 A m-2, and the power density is 4.2 × 10-5 W m-2. During both the motion detecting and gas sensing processes, no external electricity power is needed. The triboelectric signal can be treated as not only the sensing signal but also the power source for driving the device. The working mechanism is based on surface-triboelectric coupling effect. The present results can promote the development of self-powered wearable electronics.

12.
Nanotechnology ; 29(7): 075501, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29256443

RESUMO

A new self-powered wearable gustation electronic skin for mimicking taste buds has been realized based on enzyme-modified/ZnO nanowire arrays on patterned-electrode flexible substrate. The e-skin can actively taste beverages or fruits without any external electric power. Through the piezoelectric-enzymatic reaction coupling effect, the nanowires can harvest the mechanical energy of body movement and output piezoelectric signal. The piezoelectric output is significantly dependent on the concentration of target analyte. The response for detecting 2 × 10-2 M ascorbic acid (ascorbate acid oxidase@ZnO) is up to 171.747, and the selectivity is high. The response for detecting 50% alcohol (alcohol oxidase@ZnO) is up to 45.867. Our results provide a new research direction for the development of multifunctional e-skin and expand the study scope for self-powered bionic systems.


Assuntos
Oxirredutases do Álcool/metabolismo , Ascorbato Oxidase/metabolismo , Fontes de Energia Elétrica , Papilas Gustativas/fisiologia , Paladar/fisiologia , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais , Humanos , Óxido de Zinco/química
13.
BMC Cancer ; 17(1): 857, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246127

RESUMO

BACKGROUND: Primary liver cancer is a lethal malignancy with a high mortality worldwide. Currently, sorafenib is the most effective molecular-targeted drug against hepatocellular carcinoma (HCC). However, the sorafenib resistance rate is high. The molecular mechanism of this resistance has not been fully elucidated. High mobility group box 1 (HMGB1) is a multifaceted protein that plays a key role in the proliferation, apoptosis, metastasis and angiogenesis of HCC cells. In addition, HMGB1 has been suggested to contribute to chemotherapy resistance in tumours, including lung cancer, osteosarcoma, neuroblastoma, leukaemia, and colorectal cancer. This study investigated the association between HMGB1 and sorafenib resistance in HCC. METHODS: HepG2 cells with HMGB1 knockdown or overexpression were generated. The efficacy of sorafenib in these cells was tested using flow cytometry and a cell counting assay. The subcellular localization of HMGB1 in HepG2 cells following sorafenib treatment was measured by western blotting and confocal microscopy. A murine subcutaneous HCC model was generated to examine the association between HMGB1 and the sensitivity of sorafenib treatment. RESULTS: The HMGB1 knockdown cells exhibited a significantly higher apoptotic level and lower cell viability than the normal HMGB1 expressing cells following the sorafenib treatment. In addition, the cell viability observed in the HMGB1 overexpressing cells was higher than that observed in the control cells following the sorafenib intervention. Sorafenib had a better tumour inhibition effect in the HMGB1 knockdown group in vivo. The amount of mitochondrial HMGB1 decreased, while the amount of cytosolic HMGB1 increased following the exposure to sorafenib. Altogether, HMGB1 translocated from the mitochondria to the cytoplasm outside the mitochondria following the exposure of HepG2 cells to sorafenib. CONCLUSIONS: A novel potential role of HMGB1 in the regulation of sorafenib therapy resistance in HCC was observed. The knockdown of HMGB1 restores sensitivity to sorafenib and enhances HepG2 cell death, while HMGB1 overexpression blunts these effects. The translocation of HMGB1 from the mitochondria to the cytosol following sorafenib treatment provides new insight into sorafenib resistance in HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Proteína HMGB1/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Animais , Carcinoma Hepatocelular/patologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Regulação para Baixo , Técnicas de Silenciamento de Genes , Proteína HMGB1/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Transporte Proteico , RNA Interferente Pequeno/metabolismo , Sorafenibe , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Nanotechnology ; 27(37): 375704, 2016 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-27502445

RESUMO

Highly-efficient sono-solar-induced degradation of organic dye by the piezophototronic/photocatalytic coupling effect of FeS/ZnO nanoarrays was achieved. A steel screen was used as the substrate for supporting FeS/ZnO nanoarrays, and the nanoarrays were vertically and uniformly grown on the substrate via a wet-chemical route. Under ultrasonic and solar irradiation, FeS/ZnO nanoarrays have high sono-photocatalytic activity for degrading methylene blue in water. The photogenerated carriers can be separated by a piezoelectric field and a built-in electric field, resulting in a low recombination rate and high photocatalytic efficiency. The piezophototronic and photocatalytic effects were coupled together. The experimental/theoretical data indicate that this novel wastewater treatment can co-use mechanical and solar energy in nature, and so is a promising technology for environment improvement.

15.
Phys Chem Chem Phys ; 17(3): 2121-6, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25484127

RESUMO

Room-temperature self-powered H2S sensing with high response and selectivity has been realized from a Cu-ZnO nanowire nanogenerator. Upon exposure to 1000 ppm H2S at room temperature, the piezoelectric output voltage of the device (5 at% Cu-ZnO) under compressive force decreases from 0.552 (in dry air) to 0.049 V, and the response is up to 1045, over 8 times larger than that of undoped ZnO nanowires. The selectivity against H2S is also very high at room temperature. The enhanced room-temperature H2S sensing performance can be attributed to the coupling of the piezoelectric screening effect of ZnO nanowires and the synergistic effect of the Cu dopant. This study should stimulate research into designing a new gas sensor for detecting toxic gases at room temperature.

16.
Phys Chem Chem Phys ; 17(16): 10856-60, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25820663

RESUMO

Highly sensitive humidity sensing has been realized from a Cd-doped ZnO nanowire (NW) nanogenerator (NG) as a self-powered/active gas sensor. The piezoelectric output of the device acts not only as a power source, but also as a response signal to the relative humidity (RH) in the environment. The response of Cd-ZnO (1 : 10) NWs reached up to 85.7 upon exposure to 70% relative humidity, much higher than that of undoped ZnO NWs. Cd dopant can increase the number of oxygen vacancies in the NWs, resulting in more adsorption sites on the surface of the NWs. Upon exposure to a humid environment, a large amount of water molecules can displace the adsorbed oxygen ions on the surface of Cd-ZnO NWs. This procedure can influence the carrier density in Cd-ZnO NWs and vary the screening effect on the piezoelectric output. Our study can stimulate a research trend on exploring composite materials for piezo-gas sensing.

17.
Epigenetics Chromatin ; 17(1): 15, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725075

RESUMO

UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT , Neoplasias , Processamento de Proteína Pós-Traducional , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias/metabolismo , Neoplasias/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Metilação de DNA , Animais , Ubiquitinação , Regulação Neoplásica da Expressão Gênica
18.
Cell Oncol (Dordr) ; 47(1): 245-258, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37676377

RESUMO

PURPOSE: Platinum-based chemotherapy remains a standard-of-care for most patients with advanced non-small cell lung cancer (NSCLC). DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. Previous studies have reported that RanBPM has been involved in various cellular processes such as DDR by interacting with multiple proteins. However, the underlying mechanism remains unclear. METHODS: NSCLC tissue microarrays were used for assessing the expression of RanBPM by immunohistochemical staining. The roles of RanBPM in the DDR of NSCLC progression was examined in in vitro cell lines and in vivo animal models. The regulation of RanBPM on protein stability and ubiquitination levels were investigated by immunoblots and in vivo ubiquitylation assay. RESULTS: The level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation. Mechanistically, RanBPM protein physically interacts with p21, and RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. RanBPM silencing significantly decreased p21 protein level. Conversely, RanBPM overexpression led to the accumulation of endogenous p21 protein regardless of p53 status. Functionally, RanBPM regulates DDR in a p21-dependent manner. Furthermore, DNA damage significantly promoted the nuclear translocation of RanBPM protein through ATM signaling pathways. CONCLUSION: RanBPM is a novel regulator of P21 protein stability, and plays a critical role in the regulation of DDR.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Pulmonar de Células não Pequenas , Inibidor de Quinase Dependente de Ciclina p21 , Proteínas do Citoesqueleto , Neoplasias Pulmonares , Proteínas Nucleares , Animais , Humanos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Dano ao DNA , Reparo do DNA , Neoplasias Pulmonares/genética , Proteínas Nucleares/metabolismo , Tioléster Hidrolases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo
19.
J Cell Biol ; 222(11)2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37728657

RESUMO

UHRF1 is an epigenetic coordinator bridging DNA methylation and histone modifications. Additionally, UHRF1 regulates DNA replication and cell cycle, and its deletion induces G1/S or G2/M cell cycle arrest. The roles of UHRF1 in the regulation of G2/M transition remain poorly understood. UHRF1 depletion caused chromosome misalignment, thereby inducing cell cycle arrest at mitotic metaphase, and these cells exhibited the defects of spindle geometry, prominently manifested as shorter spindles. Mechanistically, UHRF1 protein directly interacts with EG5, a kinesin motor protein, during mitosis. Furthermore, UHRF1 induced EG5 polyubiquitination at the site of K1034 and further promoted the interaction of EG5 with spindle assembly factor TPX2, thereby ensuring accurate EG5 distribution to the spindles during metaphase. Our study clarifies a novel UHRF1 function as a nuclear protein catalyzing EG5 polyubiquitination for proper spindle architecture and faithful genomic transmission, which is independent of its roles in epigenetic regulation and DNA damage repair inside the nucleus. These findings revealed a previously unknown mechanism of UHRF1 in controlling mitotic spindle architecture and chromosome behavior and provided mechanistic evidence for UHRF1 deletion-mediated G2/M arrest.


Assuntos
Epigênese Genética , Pontos de Checagem da Fase G2 do Ciclo Celular , Cinesinas , Fuso Acromático , Ubiquitina-Proteína Ligases , Apoptose , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Mitose , Humanos , Ubiquitina-Proteína Ligases/genética , Cinesinas/genética , Ubiquitinação , Dano ao DNA , Cromossomos/genética
20.
Cell Death Discov ; 9(1): 367, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37788997

RESUMO

PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265. Phosphorylation is required for the maintenance of UHRF1 protein stability by recruiting a deubiquitinase USP7. Conversely, PLK1 inhibition decreases UHRF1 protein interaction with USP7 and activates the ubiquitin-proteasome pathway, thereby accelerating UHRF1 protein degradation. UHRF1 degradation decreases the recruitment of DNMT1 to chromatin, and decreases the level of genome-wide DNA methylation, thereby elevating the expression of tumor suppressor genes and decreasing cell viability. We here presented the first report on the novel role of PLK1 in DNA methylation maintenance through UHRF1-DNMT1 pathway, and revealed a novel anticancer mechanism of PLK1 inhibitors.

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