检索结果-南通市图书馆

skp2 attenuates NF-κB signaling by mediating IKKβ degradation through autophagy

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2018年第3期10卷 205-215页

作者： Kunpeng Liu Lei Zhang Qiang Zhao Zhiyao Zhao Feng Zhi Yunfei Qin Jun Cui Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou 510006 China Organ Transplant Center The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China Modern Medical Research Center Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou 213000 China Guangdong Provincial Key Laboratory of Liver Disease CeU-Gene Therapy Translational Medicine Research Center The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630 China

NF-κB signaling controls a large set of physiological processes ranging from inflammatory responses to cell death. Its activation is tightly regulated through controlling the activity and stability of multiple signaling components. Here, we identify that NF-κB activation is suppressed by an F-box protein, S-phase kinase associated protein 2 （skp2）. skp2 deficiency enhanced NF-κB activation as well as the production of inflammatory cytokines. In addition, skp2 potently blocked the NF-κB activation at the κB kinase （IKIO level. Mechanistic study further revealed that skp2 functions as an adaptor to promote an interaction between active IKKβ and the autophagic cargo receptor p62 to mediate IKKβ degradation via selective autophasy. These findings identify a previously unrecognized role of skp2 in NF-κB activation by which skp2 acts as a secondary receptor to assist IKKβ delivery to autophagosomes for degradation in a p62-dependent manner.

关键词： skp2 IKKβ NF-κB activation autophagy inflammation

skp2 is a novel regulator of LSD1 expression and function in gastric cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genes & Diseases 2023年第6期10卷 2267-2269页

作者： Moges Dessale Asmamaw Li-Rong Zhang Hong-Min Liu Xiao-Jing Shi Ying Liu Department of Pharmacology School of Basic Medical SciencesState Key Laboratory for Esophageal Cancer Prevention and TreatmentZhengzhou UniversityZhengzhouHenan 450001China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhouHenan 450001China Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaZhengzhouHenan 450001China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Henan Engineering Research Center for Application&Translation of Precision Clinical Pharmacy ZhengzhouHenan 450052China

S-phase kinase-associated protein 2(skp2)is a well-characterized oncoprotein localized mainly in the nucleus and *** is an integral component of SCFskp2 E3 ubiquitin ligase complex which confers substrate selectivity to the ligase by specifically targeting a distinct set of proteins destined for proteasomal degradation such as p21,p27,cyclin E,and c-Myc.1 skp2 is crucial in a multitude of cellular processes including cell cycle,cell proliferation,apoptosis,differentiation,and ***,despite its immense and well-established role in ubiquitin-proteasome system-mediated protein turnover,much is unknown about the function of skp2 independent of the ubiquitination ***,skp2 has been reported to regulate RhoA gene transcription and the p300 signaling pathway in an E3 ligase-independent manner.2Moreover,skp2 also acts as a cofactor for c-Myc-regulated gene expression.

关键词： skp2 expression. function

The steady-state level of CDK4 protein ms regulated by antagonistic actions between PAQR4 and skp2 and involved in tumorigenesis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2017年第5期9卷 409-421页

作者： Lin Wang RuiZhang Xue You Huanhuan Zhang Siying Wei Tingting Cheng Qianqian Gao ZhenzhenWang Yan Chen CAS Key Laboratory of Nutrition and Metabolism Institute for Nutritional Sciences Shanghai Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China Cancer Molecular Diagnostic Core Laboratory Tianjin Medical University Cancer Institute and Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060 China School of Life Sciences and Technology ShanghaiTech University Shanghai 200031 China Department of Clinical Medicine Tongji University Shanghai 200092 China Department of Clinical Medicine Tongji University Shanghai 200092 China

CDK4 is crucial for Gl-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cycUns are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and skp2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, skp2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. importantly, PAQR4 and skp2 bind to the same region in CDK4, and PAQR4 competes with skp2 for the binding, thereby abrogating skp2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4-deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and skp2, contributing to modulation of cell proliferation and tumorigenesis.

关键词： CDK4 PAQR4 skp2 ubiquitination protein degradation tumorigenesis

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase skp2 in lung epithelial cells

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Medicine 2021年第2期15卷 252-263页

作者： Guizhen Wang Qun Zhao Hui Zhang Fan Liang Chen Zhang Jun Wang Zhenyin Chen Ran Wu Hong Yu Beibei Sun Hua Guo Ruie Feng Kaifeng Xu Guangbiao Zhou State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing 100101China Hubei University of Medicine Shiyan 442000China Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of Pulmonary and Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Guizhou University School of Medicine Guiyang 550025China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%–18.5%of hospitalized adults,calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 ***,we show that cigarette smoke extract(CSE)and carcinogen benzo(a)pyrene(BaP)increase ACE2 mRNA but trigger ACE2 protein *** induces an aryl hydrocarbon receptor(AhR)-dependent upregulation of the ubiquitin E3 ligase skp2 for ACE2 ***2 in lung tissues of non-smokers is higher than in smokers,consistent with the findings that tobacco carcinogens downregulate ACE2 in *** carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the *** that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and skp2 is an oncoprotein,tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

关键词： SARS-CoV-2 tobacco smoke benzo(a)pyrene ACE2 skp2

Nobiletin downregulates the skp2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma

在线全文

学校读者我要写书评

暂无评论

Cancer Biology & Medicine 2021年第1期18卷 227-244页

作者： Tingting Chen Liu Liu Yonghong Zou Xiaoyan Hu Wenfeng Zhang Tao Zhou Xi Luo Weihua Fu Jie Xu Department of Urology Xinqiao Hospital of Army Medical UniversityChongqing 400037China Department of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430040China Department of Reproductive Medicine Ji’an Central People’s HospitalJi'an 343100China Department of Infectious Disease the First Affiliated HospitalNanchang UniversityNanchang 330001China Department of Oncology Southwest Hospital of Army Medical UniversityChongqing 400038China

Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic ***,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still ***:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in *** nude mouse model was used to test the efficacy of nobiletin alone or in combination with ***:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC ***,nobiletin decreased skp2 protein expression by reducing its transcriptional *** downregulated skp2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher skp2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo ***:Nobiletin downregulated the skp2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.

关键词： Nobiletin skp2 palbociclib synergistic renal cell carcinoma

17β-Estradiol Regulates skp2 Expression in Cultured Immature Boar Sertoli Cells Mainly via Estrogen Receptor β,cAMP-PKA and ERK1/2

在线全文

学校读者我要写书评

暂无评论

Journal of Integrative Agriculture 2014年第4期13卷 827-836页

作者： WANG Xian-zhong ZHU Feng-wei WANG Yong WANG Yi ZHANG Jiao-jiao ZHANG Jia-hua Chongqing Key Laboratory of Forage & Herbivore College of Animal Science and TechnologySouthwest University

Estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （skp2） plays a central role in mammalian cell cycle progression. The objective of this study was to determine whether 17β-estradiol can regulate the expression of skp2, and the Sertoli cell cycle, via estrogen receptor β （ERβ）, the cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA） and extracellular signal-regulated kinase （ERK1/2） pathway. When cultured immature boar Sertoli cells were treated with 17β-estradiol, a time-dependent increase in skp2 mRNA and protein level was observed by real-time PCR and Western blot, and 17β-estradiol activity peaked at 30 min. Treatment with ICI182780 and ERβ antagonist reduced 17β-estradiol-induced expression of skp2 and proliferating cell nuclear antigen （PCNA）, while increasing the protein concentration of p27kip1. However, the effect of ERa antagonist on these parameters was lower than that of ICI 182780 and ERβ. Forskolin had a similar effect as 17β-estradiol on the expression of skp2, PCNA and p27kip1, Rp-cAMP, H-89 and U0126 treatment reduced 17β-estradiol-induced changes, while H-89 also inhibited ERK1/2 activation. Therefore, 17β-estradiol mainly regulates skp2 mRNA and protein expression via ERβ-cAMP-PKA and ERK1/2 activation. skp2 and PCNA expression were positively correlated, while increased skp2 expression likely resulted in p27kip1 degradation.

关键词： 17β-estradiol Sertoli cell skp2 estrogen receptor cAMP-PKA ERK1/2

Chondroitin Polymerizing Factor (CHPF) promotes cell proliferation and tumor growth in human osteosarcoma by inhibiting skp2's ubiquitination while activating the AKT pathway

在线全文

学校读者我要写书评

暂无评论

Genes & Diseases 2023年第5期10卷 2125-2136页

作者： Yi Shen Jun Li Dan Peng Lele Liao Xia Chen Weiye Zhong Zicheng Liu Chao Yu Yuanliang Sun Department of Orthopaedics The Second Xiangya Hospital of Central South UniversityChangshaHunan 410000China Department of Spine Surgery Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China

Osteosarcoma is a common malignant tumor occurring in children and young adults. Chondroitin sulfate (CS) participates in cell adhesion, cell division, and the formation of neural networks in the body, the biosynthesis of which requires the participation of glycosyltransferases. CHPF, a glycosyltransferase, plays a role in the extension of CS. Recently, CHPF's biological roles and functional importance in human diseases including malignant tumors have been widely discussed. However, whether CHPF is involved in osteosarcoma development and growth has not been revealed. The present work aimed to investigate the expression levels, functional significance and molecular mechanism of CHPF in osteosarcoma progression. Our results revealed that CHPF is strongly expressed in osteosarcoma tissues and cells. Furthermore, CHPF serves as a tumor promoter in the development and progression of osteosarcoma through enhancing cell proliferation and migration while suppressing apoptosis. Exploration of the mechanism by which CHPF promotes osteosarcoma indicated that CHPF promotes osteosarcoma through counteracting skp2's ubiquitination and activating the Akt signaling pathway. For the first time, we clarified the roles of CHPF in osteosarcoma, and our results suggested that CHPF might be a novel therapeutic target in the treatment strategies for osteosarcoma.

关键词： Akt signaling pathway CHPF Osteosarcoma skp2 Ubiquitination

ZNF292 suppresses proliferation of ESCC cells through ZNF292/skp2/P27 signaling axis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Cancer Research 2021年第6期33卷 637-648页

作者： Wei Gong Jiancheng Xu Guangchao Wang Dan Li Qimin Zhan State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:Increasing evidence has demonstrated that ZNF292 plays a suppressive role in cancer,however,little is known about its function and exact mechanism in esophageal squamous cell carcinoma(ESCC).Methods:Bioinformatic analysis and immunohistochemistry(IHC)were performed to analyze the role of ZNF292 in affecting the prognosis of *** proliferation and colony formation ability assays were performed to analyze cell growth after inferring the expression of *** cytometry was used to analyze changes in the cell cycle upon the depletion of *** real-time polymerase chain reaction(q RT-PCR)and western blot analysis were used to determine the alteration of cell cycle related RNAs and proteins after knocking down ***-132,cycloheximide(CHX)treatment experiments were performed to analyze the change and half-life time of P27 after knockdown of *** immunoprecipitation(Ch IP)and luciferase reporter assays were used to analyze the transcriptional regulation of skp2 by ***:We report that low expression of ZNF292 is associated with poor prognosis,and ZNF292 emerges to be highly expressed in adjacent and normal tissues rather than tumor tissues in *** of ZNF292 significantly boosts cell growth and S phase entry in ESCC ***292 depletion will decrease the expression and half-life time of P27,while knockdown of skp2 will result in elevated expression of ***292 can bind to the promoter region of skp2,and knockdown of ZNF292 will boost the expression of ***:Knockdown of ZNF292 mediates G1/S cell cycle procession by activating skp2/P27 signaling in ESCC ***292 knockdown promotes skp2 expression at the transcriptional level,thereby boosting P27 ubiquitin-degradation,and eventually facilitating the S phase entrance.

关键词： ZNF292 cell cycle skp2 ESCC

Regulation of skp2 protein stability by heat shock protein 90 chaperone machinery

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2021年第8期6卷 2331-2333页

作者： Lili Cai Lihui Li Xihui Chen Lijun Jia Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

Dear Editor,S phase kinase-associated protein 2(skp2),a substrate recognition component of the SCFskp2 ubiquitin ligase complex,plays an oncogenic role in tumorigenesis by targeting a variety of tumor suppressors(e.g.,p21,p27,and p130)for ubiquitina-tion and subsequent degradation.1 As a well-characterized oncoprotein,the aberrant expression and dysregulation of skp2 are frequently observed in different human *** its critical role in governing tumorigenesis and progression,skp2 has emerged as a potential pharmacological target for anticancer therapy.

关键词： skp2 suppressor shock