Article
Multidisciplinary Sciences
Justus F. Graef, Ivan Mikicic, Xiaofei Ping, Claudia Scalera, Katharina Mayr, Lukas S. Stelzl, Petra Beli, Sebastian A. Wagner
Summary: PPM1D is a protein phosphatase regulated by p53, involved in modulating the DNA damage response. It is frequently mutated in cancer. By using chemical inhibition and mass spectrometry-based phosphoproteomics, the substrates of PPM1D were identified upon induction of DNA double-strand breaks. It was found that PPM1D partially counteracts the ATM/ATR/DNA-PK signaling pathway. The targeted phosphorylation sites of PPM1D are characterized by a specific amino acid sequence motif.
Article
Biochemistry & Molecular Biology
Malissa Fenton, Wade Borcherds, Lihong Chen, Asokan Anbanandam, Robin Levy, Jiandong Chen, Gary Daughdrill
Summary: The binding of p53 to MDMX requires two short-linear motifs, WW and WF, which compete for the binding site on MDMX. The WW motif forms a helical structure when bound to the p53 binding domain of MDMX. Isothermal titration calorimetry studies showed that the WW motif is a stronger inhibitor of p53 binding than the WF motif when linked to p53BD by a natural disordered linker. Both motifs also bind to the DNA binding domain of p53, overlapping with the DNA binding site.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Jiyeon Leem, Guang-Yu Bai, Jeong Su Oh
Summary: Maintaining genome integrity in germ cells is crucial for successful fertilization and embryo development. This study showed that inhibiting WIP1 activity enhances zygotic repair of paternal DNA damage, improving the development and genome activation in zygotes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Shantanu Gupta, Pritam Kumar Panda, Ronaldo F. Hashimoto, Shailesh Kumar Samal, Suman Mishra, Suresh Kr Verma, Yogendra Kumar Mishra, Rajeev Ahuja
Summary: Transfection of tumor suppressor miRNAs, such as miR-34a, miR-449a, and miR-16, can regulate apoptosis, senescence, and autophagy in cancer cells. However, the specific functions of miR-34a and miR-449a in autophagy and the cooperative or individual roles of these three miRNAs in the functional G1/S checkpoint signaling pathways in HeLa cells remain unknown. This study presents a synthetic Boolean network illustrating the regulatory effects of these miRNAs and demonstrates their advanced role in cervical cancer signaling pathways.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Miaoqin Chen, Weikai Wang, Shiman Hu, Yifan Tong, Yiling Li, Qi Wei, Lei Yu, Liyuan Zhu, Yiran Zhu, Leiming Liu, Zhenyu Ju, Xian Wang, Hongchuan Jin, Lifeng Feng
Summary: High expression of WIP1 is associated with poor prognosis in patients with HCC. Inhibition of WIP1 and PARP induces synthetic lethality in HCC by augmenting DNA damage.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Oncology
Shunsuke Hanaki, Makoto Habara, Takahiro Masaki, Keisuke Maeda, Yuki Sato, Makoto Nakanishi, Midori Shimada
Summary: The study uncovered that NIPP1 functions as a modulator of E2F1 target genes by linking PKA and PP1γ during DNA damage, playing a crucial role in cell proliferation.
Article
Obstetrics & Gynecology
Kashmira Bane, Junita Desouza, Diksha Shetty, Prakash Choudhary, Shalaka Kadam, R. R. Katkam, Gwendolyn Fernandes, Raj Sawant, Uddhavraj Dudhedia, Neeta Warty, Anahita Chauhan, Uddhav Chaudhari, Rahul Gajbhiye, Geetanjali Sachdeva
Summary: The study indicates that the DNA damage response is dysregulated in the eutopic endometrium of women with endometriosis, with higher expression of DDR genes compared to those without the disease. Additionally, DNA repair genes are also up-regulated in the eutopic endometrium of women with endometriosis.
HUMAN REPRODUCTION
(2021)
Article
Chemistry, Multidisciplinary
Paramesh Jangili, Na Kong, Ji Hyeon Kim, Jun Zhou, Haijun Liu, Xingcai Zhang, Wei Tao, Jong Seung Kim
Summary: This study presents a novel multifunctional construct, M1, that specifically targets the DNA damage response in cancer cells. M1 combines a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor with a GSH-sensitive linker, and is activated in the mitochondria to induce mitochondria-mediated apoptosis. The inhibition of PP2A is highlighted as important for the therapeutic potential in FUDR/5-fluorouracil (5-FU) therapy, and HCT116 xenograft-bearing mice with a low response to 5-FU show significant effects with M1, emphasizing the importance of targeting DNA damage response using tumor-specific microenvironment-activatable systems.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Food Science & Technology
Ying Wang, Xin Li, Dequan Zhang, Zheng Li, Baocai Xu, Jie Zhu
Summary: This study investigated the effect of phosphorylation on titin degradation and found that treatment with alkaline phosphatase could make titin more susceptible to degradation by mu-calpain.
FOOD SCIENCE AND HUMAN WELLNESS
(2023)
Article
Biochemistry & Molecular Biology
Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Virgilia Macias, Eileen Brister, Jay Sonalkar, Linyuan Shen, Jaba Mitra, Taekjip Ha, Andre Kajdacsy-Balla, Kannanganattu V. Prasanth, Supriya G. Prasanth
Summary: The smallest subunit of the human Origin Recognition Complex, hOrc6, is necessary for DNA replication progression and is involved in mismatch repair during S-phase. The molecular mechanisms of how hOrc6 regulates DNA replication and damage response are still unclear. Elevated levels of Orc6 and reduced phosphorylation at Thr229 are observed in colorectal cancers, and this may lead to uncontrolled cell proliferation. Based on these findings, DNA-damage-induced hOrc6-pThr229 phosphorylation during S-phase may facilitate ATR signaling, halt fork progression, and promote efficient repair to prevent tumorigenesis.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Biology
Felipe C. Ribeiro, Danielle Cozachenco, Luana Heimfarth, Juliana T. S. Fortuna, Guilherme B. de Freitas, Jorge M. de Sousa, Soniza V. Alves-Leon, Renata E. P. Leite, Claudia K. Suemoto, Lea T. Grinberg, Fernanda G. De Felice, Mychael V. Lourenco, Sergio T. Ferreira
Summary: Multiple research models suggest that the function and synaptic localization of proteasomes, intracellular machineries involved in protein degradation, are impaired in the brains affected by Alzheimer's disease.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Benjamin R. Stromberg, Mayank Singh, Adrian E. Torres, Amy C. Burrows, Debjani Pal, Christine Insinna, Yosup Rhee, Andrew S. Dickson, Christopher J. Westlake, Matthew K. Summers
Summary: The deubiquitinating enzyme USP37 is required beyond S-phase entry to promote the efficiency and fidelity of replication. Depletion of USP37 leads to increased replication stress and DNA damage, reduced cellular proliferation, and increased sensitivity to agents that induce replication stress. USP37 stabilizes checkpoint kinase 1 to ensure proper function and plays a crucial role in regulating cell proliferation and genome stability.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Zhipeng Hong, Tao Liu, Lingfeng Wan, Pengyan Fa, Pankaj Kumar, Yanan Cao, Chandra Bhushan Prasad, Zhaojun Qiu, Joseph Liu, Hongbing Wang, Zaibo Li, Qi-En Wang, Peixuan Guo, Deliang Guo, Ayse S. Yilmaz, Lanchun Lu, Ioanna Papandreou, Naduparambil K. Jacob, Chunhong Yan, Xiaoli Zhang, Qing-Bai She, Zhefu Ma, Junran Zhang
Summary: This study investigates the importance of Squalene epoxidase (SQLE) in breast cancer and non-small cell lung cancer (NSCLC) and reveals its potential as a novel tumor-specific radiosensitizer. The study found that SQLE is frequently overexpressed in these cancers and its inhibition enhances cancer cell radiosensitivity and sensitivity to PARP inhibition. Furthermore, SQLE inhibition disrupts homologous recombination and promotes endoplasmic reticulum stress response. Repurposing existing SQLE-inhibiting drugs may provide new cancer treatments.
Article
Biochemistry & Molecular Biology
Radka Storchova, Matous Palek, Natalie Palkova, Pavel Veverka, Tomas Brom, Ctirad Hofr, Libor Macurek
Summary: Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. PPM1D also targets substrates at chromatin and contributes to the control of DNA damage response and DNA repair. The interaction between PPM1D and the shelterin complex at telomeres, as well as the role of TRF2 phosphorylation in regulating DNA repair, were identified in this study.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Agriculture, Multidisciplinary
Chi Ren, Xubo Song, Yu Dong, Chengli Hou, Li Chen, Zhenyu Wang, Xin Li, Martine Schroyen, Dequan Zhang
Summary: The study found that phosphorylation of myofibrillar proteins catalyzed by pyruvate kinase M2 (PKM2) can inhibit protein degradation and provide a possible pathway for meat tenderization through glycolytic enzyme regulation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)