Article
Cell Biology
Mireia Palomar-Siles, Angelos Heldin, Meiqiongzi Zhang, Charlotte Strandgren, Viktor Yurevych, Jip T. van Dinter, Sem A. G. Engels, Damon A. Hofman, Susanne Ohlin, Birthe Meineke, Vladimir J. N. Bykov, Sebastiaan van Heesch, Klas G. Wiman
Summary: FUr can induce the expression of full-length p53 in tumor cells carrying R213X nonsense mutant TP53, leading to apoptosis and cell death. FUr can also restore the expression of full-length p53 in human tumor xenografts carrying TP53 R213X mutation.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Alvin Kunyao Guo, Yoko Itahana, Veerabrahma Pratap Seshachalam, Hui Ying Chow, Sujoy Ghosh, Koji Itahana
Summary: This study identified a novel interaction between TP53(R273H) and BCAR1, where BCAR1 translocates from the cytoplasm to the nucleus and binds to TP53(R273H) in a manner dependent on SRC family kinases (SFKs), promoting cancer cell invasion. High BCAR1 expression was associated with a poorer prognosis among patients with mutant TP53, highlighting the potential therapeutic approach of disrupting the TP53(R273H)-BCAR1 binding in TP53(R273H)-harbouring cancer patients.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Svein Erik Moe, Fredrik A. Erland, Siren Fromreide, Stein Lybak, Marianne Brydoy, Harsh N. Dongre, Sophia M. Dhayalan, Daniela-Elena Costea, Olav K. Vintermyr, Hans Jorgen Aarstad
Summary: This study found an association between somatic TP53 mutations and the presence of human papillomavirus (HPV) in tumors of head and neck squamous cell carcinoma (HNSCC) patients. Only 2 of 44 HPV-positive patients had TP53 mutations, while 42 of 60 HPV-negative patients had TP53 mutations. Furthermore, in HPV-negative patients, a higher percentage of somatic TP53 mutations were found in the TP53 R72 polymorphism cohort compared to the TP53 P72 cohort.
Article
Cell & Tissue Engineering
Ming Luo, Mingyang Huang, Ningning Yang, Yufan Zhu, Peng Huang, Zhujun Xu, Wengang Wang, Lin Cai
Summary: Osteosarcoma (OS) is a pediatric bone tumor with high heterogeneity. The discrepancy in tumorigenicity among OS cell lines is not fully understood. In this study, we investigated the potential role of mechanotransduction in OS tumorigenicity using in vitro and in vivo models. We found impaired mechanosensing and downregulation of rigidity-sensing proteins in transformed OS cells, as well as a novel TP53 mutation (R156P) that inhibits rigidity sensing. Our findings suggest that rigidity-sensing components play a fundamental role in OS tumorigenicity and mutant TP53 serves as an executor for malignant programs.
Article
Chemistry, Analytical
Pengcheng Sun, Kai Niu, Haiying Du, Ruixin Li, Jiping Chen, Xianbo Lu
Summary: The study presents an electrochemical gene-sensor capable of rapidly and sensitively detecting tumor related TP53 gene mutation hotspots. The biosensor achieves high sensitivity and specificity, making it a powerful tool for early diagnosis and detection of cancer.
Article
Biochemistry & Molecular Biology
Allison Duncan, Darryl Nousome, Randy Ricks, Huai-Ching Kuo, Lakshmi Ravindranath, Albert Dobi, Jennifer Cullen, Shiv Srivastava, Gregory T. Chesnut, Gyorgy Petrovics, Indu Kohaar
Summary: Growing evidence suggests that genetics plays a role in prostate cancer susceptibility and severity. This study investigated the association between TP53 gene SNPs and clinico-pathological features of prostate cancer in African American (AA) and Caucasian (CA) men. The results showed ancestral differences in allele frequencies, with the TP53 Arg72Pro SNP associated with a shorter time to biochemical recurrence.
Article
Biochemistry & Molecular Biology
Chiara Ambrosini, Eliana Destefanis, Eyemen Kheir, Francesca Broso, Federica Alessandrini, Sara Longhi, Nicolo Battisti, Isabella Pesce, Erik Dassi, Gianluca Petris, Anna Cereseto, Alessandro Quattrone
Summary: BOOST is a gene-editing approach that rescues haploinsufficiency by modifying specific single nucleotides in the Kozak sequence. It has been found that many haploinsufficient genes are regulated by suboptimal Kozak sequences, and by changing these sequences, gene translation can be enhanced to treat these diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Sarah R. Oikemus, Edith L. Pfister, Ellen Sapp, Kathryn O. Chase, Lori A. Kennington, Edward Hudgens, Rachael Miller, Lihua Julie Zhu, Akanksh Chaudhary, Eric O. Mick, Miguel Sena-Esteves, Scot A. Wolfe, Marian DiFiglia, Neil Aronin, Michael H. Brodsky
Summary: Huntington's disease is a neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin gene. Inactivation of the mutant allele using CRISPR-Cas9 gene editing offers a potential therapeutic approach, and targeting a protein coding sequence containing a single nucleotide polymorphism allows for allele-specific inactivation. This study successfully demonstrated allele-selective reduction of mutant huntingtin protein in a mouse model of the disease.
HUMAN GENE THERAPY
(2022)
Review
Oncology
Zequn Zheng, Yongfei Song
Summary: Initially identified as an actin-binding protein, Synaptopodin 2 (SYNPO2) is not only involved in microfilament assembly but also performs diverse functions in cancer, predominantly acting as a tumor suppressor. Its abnormal expression affects autophagy generation and chaperone-mediated autophagy, and it regulates tumor growth and metastasis through specific signaling pathways. Additionally, SYNPO2's subcellular localization, promoter methylation, and genetic variations have been associated with cancer progression, suggesting its potential as a prognostic or diagnostic target.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Angelos Heldin, Matko Cancer, Mireia Palomar-Siles, Susanne Ohlin, Meiqiongzi Zhang, Alexander Sun-Zhang, Anna Mariani, Jianping Liu, Vladimir J. N. Bykov, Klas G. G. Wiman
Summary: The TP53 and PTEN tumour suppressor genes are frequently inactivated by nonsense mutations in human tumours. In this study, two novel compounds were identified that can induce translational readthrough and restore the expression of full-length p53 protein in cells with TP53 nonsense mutations. Compound C47 showed synergy with G418, a known readthrough inducer, while compound C61 synergized with eRF3 degraders CC-885 and CC-90009. Furthermore, compound C47 also demonstrated potent induction of full-length PTEN protein in cells with different PTEN nonsense mutations. These findings may have implications for the development of targeted cancer therapy by pharmacologically inducing translational readthrough.
Article
Biochemistry & Molecular Biology
Usama, Zahid Khan, Aktar Ali, Masaud Shah, Muhammad Imran
Summary: Vitamin D (VD) can be produced by the skin or obtained from diet, and deficiency of VD is associated with various risk factors including mutations and modifications in its transport protein VDBP or GC-globulin. Two common single nucleotide polymorphisms create three isoforms of VDBP, and the study investigates the effect of these mutations on conformational changes and VD-binding affinity. The findings reveal the importance of glycation in stabilizing the protein structure and propose a novel mechanism in how distant mutations affect the VD interaction with VDBP.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Jing Wang, Shasha Zhang, Jiaxin Zhang, Zhongliang Zhang, Qinglong Ma, Wenkang Fu, Xiaohua Chen, Dapeng Zhao, Meie Zhao, Cuixia Di, Xiaodong Xie
Summary: This study found a significant association between PTEN gene polymorphisms and chemosensitivity in Chinese breast cancer patients, particularly in rs786204926 polymorphism. The rs786204926 mutation leads to the formation of a novel PTEN mutant, which increases chemosensitivity through the PI3K-AKT signaling pathway.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Cell Biology
Jing-Hua Yang, Han-Pil Choi, Annie Yang, Roya Azad, Fengmei Chen, Zhangsuo Liu, Kazem M. Azadzoi
Summary: A comparison of protein sequence variations between ischemic and normal bladder tissues revealed a large number of non-coded amino acid residues in bladder ischemia, potentially serving as a novel biomarker for smooth muscle dysfunction.
Article
Plant Sciences
Jared M. Simons, Tim C. Herbert, Coleby Kauffman, Marc Y. Batete, Andrew T. Simpson, Yuka Katsuki, Dong Le, Danielle Amundson, Elizabeth M. Buesche, Clifford Weil, Mitch Tuinstra, Charles Addo-Quaye
Summary: This study focuses on improving the accuracy of detecting EMS-induced mutations in a mutant population by implementing new methods, demonstrating high concordance between different variant-calling algorithms, and uncovering additional false-negative mutations. The final dataset contains a substantial increase in SNP detection, providing a valuable genetic resource for sorghum research.
Article
Obstetrics & Gynecology
Huan-Yu Liu, Shanshan Qin, Zhou Zhang, Jiahui Qi, Wei Zhang, Song-Mei Liu, Yuanzhen Zhang
Summary: This case-control study examined the effects of genetic-epigenetic interaction on Early-GDM and fetal development. The results revealed that MTHFR gene polymorphisms and cytosine modifications are involved in the development of Early-GDM and potential complications in newborns.
REPRODUCTIVE SCIENCES
(2023)
