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The role of p53 in reproduction,an unexpected function for a tumor suppressor

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Journal of Molecular Cell Biology 2019年第7期11卷 624-627页

作者： Wenwei Hu zhaohui feng Rutgers Cancer Institute of New Jersey Rutgers UniversityNew BrunswickNj 08903USA

At the beginning of the 21st century,the role of p53 as a tumor suppressor was well established;however,the function of p53 other than tumor suppression,especially its function under physiological conditions,was poorly understood.Here,we revisited the journey of a multidisciplinary team of researchers that revealed an unexpected and important function of p53 in regulating maternal reproduction at that time.This finding of p53 in maternal reproduction helped us gain important insights about the p53 protein and expanded our understanding of p53 protein functions in addition to its tumor suppressive function.This fin ding also provided a possible clue to explain the observed evolutionary selection on some alleles ofthe p53 pathway.

关键词： beginning suppressor pathway

Optimized operation scheme of flash-memory-based neural network online training with ultra-high endurance

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Journal of Semiconductors 2024年第1期45卷 33-37页

作者： Yang feng zhaohui Sun Yueran Qi Xuepeng Zhan Junyu Zhang Jing Liu Masaharu Kobayashi Jixuan Wu Jiezhi Chen School of Information Science and Engineering(ISE) Shandong UniversityQingdao 266200China Neumem Co. LtdHefei 230093China Key Laboratory of Microelectronic Devices and Integrated Technology Institute of Microelectronics of Chinese Academy of SciencesBeijing 100084China Institute of Industrial Science The University of TokyoTokyoJapan

With the rapid development of machine learning,the demand for high-efficient computing becomes more and more urgent.To break the bottleneck of the traditional Von Neumann architecture,computing-in-memory(CIM)has attracted increasing attention in recent years.In this work,to provide a feasible CIM solution for the large-scale neural networks(NN)requiring continuous weight updating in online training,a flash-based computing-in-memory with high endurance(10^(9) cycles)and ultrafast programming speed is investigated.On the one hand,the proposed programming scheme of channel hot electron injection(CHEI)and hot hole injection(HHI)demonstrate high linearity,symmetric potentiation,and a depression process,which help to improve the training speed and accuracy.On the other hand,the low-damage programming scheme and memory window(MW)optimizations can suppress cell degradation effectively with improved computing accuracy.Even after 109 cycles,the leakage current(I_(off))of cells remains sub-10pA,ensuring the large-scale computing ability of memory.Further characterizations are done on read disturb to demonstrate its robust reliabilities.By processing CIFAR-10 tasks,it is evident that~90%accuracy can be achieved after 109 cycles in both ResNet50 and VGG16 NN.Our results suggest that flash-based CIM has great potential to overcome the limitations of traditional Von Neumann architectures and enable high-performance NN online training,which pave the way for further development of artificial intelligence(AI)accelerators.

关键词： NOR flash memory computing-in-memory endurance neural network online training

Tumor suppressor p53 meets microRNAs

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分子细胞生物学报:英文版 2011年第1期3卷 44-50页

作者： zhaohui feng Cen Zhang Rui Wu Wenwei Hu Department of Radiation Oncology Cancer Institute of New JerseyUniversity of Medicine and Dentistry of New JerseyNew BrunswickNJ 08903USA Department of Pediatrics Cancer Institute of New JerseyUniversity of Medicine and Dentistry of New JerseyNew BrunswickNJ 08903USA

Tumor suppressor p53 plays a central role in tumor prevention.As a transcription factor,p53 mainly exerts its function through transcription regulation of its target genes to initiate various cellular responses.To maintain its proper function,p53 is tightly regulated by a wide variety of regulators in cells.Thus,p53,its regulators and regulated genes form a complex p53 network which is composed of hundreds of genes and their products.microRNAs(miRNAs)are a class of endogenously expressed,small non-coding RNA molecules which play a key role in regulation of gene expression at the post-transcriptional level.Recent studies have demonstrated that miRNAs interact with p53 and its network at multiple levels.p53 regulates the transcription expression and the maturation of a group of miRNAs.On the other hand,miRNAs can regulate the activity and function of p53 through direct repression of p53 or its regulators in cells.These findings have demonstrated that miRNAs are important components in the p53 network,and also added another layer of complexity to the p53 network.

关键词： p53 tumor suppression microRNA

Tumor suppressor p53 and metabolism

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Journal of Molecular Cell Biology 2019年第4期11卷 284-292页

作者： Juan Liu Cen Zhang Wenwei Hu zhaohui feng Department of Radiation Oncology Rutgers Cancer Institute of New Jersey Rutgers University State University of New Jersey New Brunswick NJ 08903 USA Department of Pharmacology Rutgers Cancer Institute of New Jersey Rutgers University State University of New Jersey New Brunswick NJ 08903 USA

p53 plays a key role in tumor suppression. The tumor suppressive function of p53 has long been attributed to its ability to induce apoptosis, cell cycle arrest, and senescence in cells. However, recent studies suggest that other functions of p53 also contribute to its role as a tumor suppressor, such as its function in metabolic regulation. p53 regulates various metabolic pathways to maintain the metabolic homeostasis of cells and adapt cells to stress. In addition, recent studies have also shown that gain-offunction (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression. Further understanding of p53 and its GOF mutants in metabolism will provide new opportunities for cancer therapy.

关键词： p53 tumor suppressor mutant p53 gain-of-function metabolism

Parkinson’s disease-associated protein Parkin: an unusual player in cancer

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Cancer Communications 2018年第1期38卷 421-428页

作者： Juan Liu Cen Zhang Wenwei Hu zhaohui feng Department of Radiation Oncology Rutgers Cancer Institute of New JerseyRutgersState University of New JerseyNew BrunswickNJ 08903USA Department of Pharmacology Rutgers Cancer Institute of New JerseyRutgersState University of New JerseyNew BrunswickNJ 08903USA

The mutation of the Parkin gene is a cause of familial Parkinson’s disease.A growing body of evidence suggests that Parkin also functions as a tumor suppressor.Parkin is an ubiquitin E3 ligase,and plays important roles in a variety of cellular processes implicated in tumorigenesis,including cell cycle,cell proliferation,apoptosis,metastasis,mitophagy and metabolic reprogramming.Here we review the role and mechanism of Parkin in cancer.

关键词： Parkin Parkinson’s disease Cancer E3 ubiquitin ligase Tumor suppressor

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睑结膜巨大恶性黑色素瘤1例

中华眼科杂志 2024年第3期60卷 278-280页

作者：张晓辉杨喆卢叶冯朝晖西安交通大学第二附属医院眼科西安710004

1例81岁左眼肿物女性患者,半年内左眼米粒大小黑色肿物体积迅速增大,延伸至眼外并伴表面糜烂出血,经活体组织检查和全身麻醉下眼眶内容物摘除术后组织病理学检查,诊断为左眼睑结膜巨大恶性黑色素瘤,组织病理类型为梭形细胞。术后未接受... 详细信息

1例81岁左眼肿物女性患者,半年内左眼米粒大小黑色肿物体积迅速增大,延伸至眼外并伴表面糜烂出血,经活体组织检查和全身麻醉下眼眶内容物摘除术后组织病理学检查,诊断为左眼睑结膜巨大恶性黑色素瘤,组织病理类型为梭形细胞。术后未接受局部放射治疗和全身化学治疗,半年后去世。

关键词：结膜肿瘤黑色素瘤预后

Gain-of-function mutant p53 in cancer progression and therapy

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Journal of Molecular Cell Biology 2020年第9期12卷 674-687页

作者： Cen Zhang Juan Liu Dandan Xu Tianliang Zhang Wenwei Hu zhaohui feng 1Department of Radiation Oncology Rutgers Cancer Institute of New JerseyRutgers-State University of New JerseyNew BrunswickNJ 08903USA

p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.

关键词： tumor suppressor p53 mutation gain-of-function tumorigenesis cancer therapy

Hot deformation characterization of as-homogenized Al-Cu-Li X2A66 alloy through processing maps and microstructural evolution

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Journal of Materials Science & Technology 2019年第10期35卷 2409-2421页

作者： Liwei Zhong Wenli Gao zhaohui feng Zheng Lu Congcong Zhu College of Materials Science and Engineering Hunan UniversityChangsha 410082China Institute of Aluminum Alloy Beijing Institute of Aeronautical MaterialsBeijing 100095China Beijing Engineering Research Center of Advanced Aluminum Alloys and Applications Beijing Institute of Aeronautical MaterialsBeijing 100095China

Uniaxial compression tests were carried out on an Al-Cu-Li alloy at a temperature range of 300–500℃ and a strain rate range of 0.001–10 s^-1. Four representative instability maps based on Gegel, AlexanderMalas(A-M), Kumar-Prasad(K-P) and Murty-Rao(M-R) criteria were constructed. Through formula deduction and microstructural observation, it can be concluded that M-R criterion is more accurate than K-P criterion, and the first two criteria are better than Gegel and A-M criteria. From a power dissipation map and a M-R instability map, the optimized processing parameters are 480–500℃/0.001–0.1 s^-1 and 420–480℃/0.1-1 s^-1. The corresponding microstructural analysis shows that dynamic recovery and partial dynamic recrystallization are main dynamic softening mechanisms. Transmission electron microscopy observation indicated that a large number of primary coarse T1(Al2 Cu Li) particles precipitated in the homogenized specimen. After deformation at 500℃, most of the primary T1 particles dissolved back into the matrix, and secondary fine T1 particles precipitated at deformation-induced dislocations, high angle grain boundaries and other dispersed particles.

关键词： deformation alloy recrystallization

Tumor suppressor p53 cross-talks with TRIM family proteins

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Genes & Diseases 2021年第4期8卷 463-474页

作者： Juan Liu Cen Zhang Xue Wang Wenwei Hu zhaohui feng Department of Radiation Oncology Rutgers Cancer Institute of New JerseyRutgers-State University of New Jersey195 Little Albany StreetNew BrunswickNJ 08903USA

p53 is a key tumor suppressor.As a transcription factor,p53 accumulates in cells in response to various stress signals and selectively transcribes its target genes to regulate a wide variety of cellular stress responses to exert its function in tumor suppression.In addition to tumor suppression,p53 is also involved in many other physiological and pathological processes,e.***.anti-infection,immune response,development,reproduction,neurodegeneration and aging.To maintain its proper function,p53 is under tight and delicate regulation through different mechanisms,particularly the posttranslational modifications.The tripartite motif(TRIM)family proteins are a large group of proteins characterized by the RING,B-Box and coiled-coil(RBCC)domains at the N-terminus.TRIM proteins play important roles in regulation of many fundamental biological processes,including cell proliferation and death,DNA repair,transcription,and immune response.Alterations of TRIM proteins have been linked to many diseases including cancer,infectious diseases,developmental disorders,and neurodegenera-tion.Interestingly,recent studies have revealed that many TRIM proteins are involved in the regulation of p53,and at the same time,many TRIM proteins are also regulated by p53.Here,we review the cross-talk between p53 and TRIM proteins,and its impact upon cellular biological processes as well as cancer and other diseases.

关键词： Cancer p53 Posttranslational modification TRIM proteins Tumor suppressor Ubiquitination