Article
Cell Biology
Salla Mattola, Elina Mantyla, Vesa Aho, Sami Salminen, Simon Leclerc, Mikko Oittinen, Kari Salokas, Jani Jarvensivu, Satu Hakanen, Teemu O. Ihalainen, Keijo Viiri, Maija Vihinen-Ranta
Summary: This study suggests that canine parvovirus capsids may use additional routes for nuclear escape, and the nuclear envelope permeability increases at the late stages of infection. Inhibition of cell cycle regulatory protein Cdk1 and pro-apoptotic protein caspase 3 can prevent the leakage of nuclear envelope, indicating the involvement of G2/M checkpoint regulation in this process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Katherine N. Lynch, Joyce F. Liu, Nikolas Kesten, Kin-Hoe Chow, Aniket Shetty, Ruiyang He, Mosammat Faria Afreen, Liping Yuan, Ursula A. Matulonis, Whitfield B. Growdon, Michael G. Muto, Neil S. Horowitz, Colleen M. Feltmate, Michael J. Worley, Ross S. Berkowitz, Christopher P. Crum, Bo R. Rueda, Sarah J. Hill
Summary: Endometrial cancers are the most common gynecologic malignancy in the United States, with TP53 mutations playing a crucial role in treatment and understanding of their vulnerabilities. Research indicates that in TP53 mutant endometrial cancers, abnormalities in cell division make them sensitive to novel therapeutic approaches, such as Aurora kinase inhibitors.
Article
Cell Biology
Vicente Lebrec, Marion Poteau, Jean-Philippe Morretton, Olivier Gavet
Summary: Researchers decoded how the DNA replication checkpoint (DRC) allows cells to enter mitosis after replication stress (RS) by developing a FRET-based Chk1 activity sensor. They found that Chk1 activity is sustained during S phase through replication origin firing and is reactivated upon RS to prevent premature mitosis.
DEVELOPMENTAL CELL
(2022)
Article
Biochemistry & Molecular Biology
Ying-Chieh Chen, Hsi-Hsien Hsieh, Hsi-Chi Chang, Hsin-Chiao Wang, Wey-Jinq Lin, Jing-Jer Lin
Summary: Cdc25B, a phosphatase, has been found to have a tumor-suppressive function in certain cancer types through a p53-dependent senescence pathway. It stabilizes p53 by binding and dephosphorylating it, leading cells to enter senescence and inhibiting cell growth. This finding sheds light on a potential therapeutic target for cancer treatment.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Siobhan O'Brien, Susan Kelso, Zachary Steinhart, Stephen Orlicky, Monika Mis, Yunhye Kim, Sichun Lin, Frank Sicheri, Stephane Angers
Summary: This study reports a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and identifies CCNL1 as a substrate of the SCF-FBXW7 E3 ligase. Defective CCNL1 accumulation resulting from FBXW7 mutation leads to shorter mitotic time. Cells with FBXW7 loss-of-function mutations are highly sensitive to treatment with a CDK11 inhibitor, suggesting a potential genetic vulnerability for cancer treatment.
Article
Oncology
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker
Summary: G2 arrest is crucial for the faithful segregation of sister chromatids, and the p53-p21 signaling pathway plays an essential role in cell lines, patient-derived cells, and colorectal cancer organoids. In arrest-defective hTERT-positive cells, the PKC epsilon failsafe mechanism is engaged. In ALT-dependent cancer cells, a distinct form of p53-independent G2 arrest is mediated by BLM and Chk1.
Article
Oncology
Soo Fern L. Lee, Jayshree L. Hirpara, Jianhua Qu, Sanjiv K. Yadav, Karishma Sachaphibulkij, Shazib Pervaiz
Summary: A novel topoisomerase II alpha inhibitor, mercaptopyridine oxide (MPO), is reported to induce cell cycle arrest and senescence through different cell cycle regulators in different cell lines. The inhibition of topoisomerase II alpha is associated with ROS-mediated activation of ATM-Chk2 kinase axis, independent of p53 function. Additionally, the interaction between topoisomerase II alpha and Chk1 is important for decatenation checkpoint activation.
Review
Pharmacology & Pharmacy
Kailin Li, Jieqiong You, Qian Wu, Wen Meng, Qiaojun He, Bo Yang, Chengliang Zhu, Ji Cao
Summary: Synthetic lethality is an effective antitumor strategy that has attracted great attention, with CDKs potentially serving as synthetic lethal factors when combined with certain oncogenes. This provides numerous antitumor treatment options and highlights the prospect of CDK inhibitors as antitumor compounds.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Oncology
Christina Hassiepen, Aashish Soni, Ines Rudolf, Vivian Boron, Sebastian Oeck, George Iliakis, Alexander Schramm
Summary: Neuroblastoma with high expression of TrkA/NTRK1 is associated with better prognosis, but the impact of TrkA/NTRK1 on radiation response is not well understood. This study found that TrkA/NTRK1-expressing cells fail to activate the G2/M cell cycle checkpoint after irradiation, leading to increased short-term cell viability. The deficient G2/M-checkpoint upon DNA damage induced by ionizing radiation in TrkA/NTRK1-activated cells suggests a potential role of NTRK signaling in checkpoint regulation and response to radiation.
Article
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gieleci, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: The cyclin-dependent kinase (CDK) family plays a critical role in regulating transcription and cell-cycle progression. Recent studies have revealed their involvement in DNA damage response (DDR) and repair, impacting the fidelity of cell division and maintenance of genomic integrity.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Oncology
Shu-Yuan Hu, Jin-Xian Qian, Shao-Ying Yang, Lisa Andriani, Li Liao, Ling Deng, Min-Ying Huang, Yin-Ling Zhang, Fang-Lin Zhang, Zhi-Min Shao, Da-Qiang Li
Summary: It was found that MORC2 is a newly identified regulator associated with cancer drug resistance. MORC2 activates the spindle assembly checkpoint, promotes mitotic progression, and affects the sensitivity of cancer cells to paclitaxel and vincristine. These findings provide a new clue for combined treatment strategy targeting MORC2 in combination with MTAs against human cancer.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Martina Galli, Laura Diani, Roberto Quadri, Alessandro Nespoli, Elena Galati, Davide Panigada, Paolo Plevani, Marco Muzi-Falconi
Summary: Symmetry breaking by cellular polarization is crucial for the cell-cycle of Saccharomyces cerevisiae cells, allowing bud emergence and growth. The morphogenesis checkpoint coordinates bud formation and cell cycle progression, with the novel role of the kinase haspin in regulating this process. Haspin monitors polarity establishment and links bud emergence to the G2/M cell cycle transition in yeast.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ying Shao, Wenming Zhang, Dongnian Du, Yi Yu, Qing Li, Xiaogang Peng
Summary: This study revealed that FAT10 promotes renal fibrosis by prolonging CHK1-mediated G2/M arrest via USP7. Inhibition of the FAT10/USP7/CHK1 axis may be a potential therapeutic approach for chronic kidney disease.
Article
Oncology
Khanh T. Do, Claire Manuszak, Emily Thrash, Anita Giobbie-Hurder, Jiani Hu, Sarah Kelland, Allison Powers, Adrienne de Jonge, Geoffrey I. Shapiro, Mariano Severgnini
Summary: The combination of CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 showed tolerability and preliminary activity in CCNE1-amplified HGSOC patients, with evidence of cytotoxic T-cell activation in patient blood samples.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Hae-Ahm Lee, Ki-Back Chu, Eun-Kyung Moon, Fu-Shi Quan
Summary: HDACi sensitizes HCC cells to oxidative stress by inducing CDK inhibitor expression, leading to inhibition of CDK4/6, FOXM1, and downstream target genes phosphorylation, ultimately causing G2/M cell cycle arrest.
Article
Cardiac & Cardiovascular Systems
David Aluja, Javier Inserte, Petronila Penela, Paula Ramos, Catalina Ribas, Miguel Angel Iniguez, Federico Mayor, David Garcia-Dorado
BASIC RESEARCH IN CARDIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Petronila Penela, Catalina Ribas, Francisco Sanchez-Madrid, Federico Mayor
CELLULAR AND MOLECULAR LIFE SCIENCES
(2019)
Article
Medicine, General & Internal
Petronila Penela, Javier Inserte, Paula Ramos, Antonio Rodriguez-Sinovas, David Garcia-Dorado, Federico Mayor
Article
Oncology
Clara Reglero, Vanesa Lafarga, Veronica Rivas, Angela Albitre, Paula Ramos, Susana R. Berciano, Olga Tapia, Maria L. Martinez-Chantar, Federico Mayor, Petronila Penela
Article
Biochemistry & Molecular Biology
Maria Gonzalez-Amor, Rocio Vila-Bedmar, Raquel Rodrigues-Diez, Rosa Moreno-Carriles, Alba C. Arcones, Marta Cruces-Sande, Mercedes Salaices, Federico Mayor, Ana M. Briones, Cristina Murga
Article
Cell Biology
Alba C. Arcones, Melanie Raquel Martinez-Cignoni, Rocio Vila-Bedmar, Claudia Yanez, Isabel Llado, Ana M. Proenza, Federico Mayor, Cristina Murga
Summary: A clear sexual dimorphism in cardiovascular disease (CVD) risk is observed, with young women having a lower incidence compared to age-matched men, but this protection is lost after menopause. Changes in G protein-coupled receptor kinase 2 (GRK2) protein levels in the heart are linked to age-related sensitivity to CVD development, with ovarian hormones playing a role in regulating GRK2 levels in the cardiac muscle, contributing to the sex-dependent dynamics of CVD risk.
Article
Cell Biology
Clara Reglero, Belen Ortiz del Castillo, Veronica Rivas, Federico Mayor Jr, Petronila Penela
Summary: This study reveals that Mdm2 E3 ligase controls centrosome separation by degrading GRK2, ensuring accurate centrosome dynamics and proper mitotic spindle functionality.
Article
Biochemistry & Molecular Biology
Maria Neves, Viviana Marolda, Federico Mayor, Petronila Penela
Summary: A better understanding of the crosstalk between key receptors and signaling pathways involved in cancer progression, specifically in breast cancer subtypes, is crucial for improving current therapies and addressing tumor microenvironment. This study examines the interplay between CXCR4/ACKR3 chemokine receptors and EGFR family signaling pathways in different breast cancer cell models and highlights their cooperation in promoting ERK1/2 activation, with potential implications for cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anais Jimenez-Reinoso, Nestor Tirado, Alba Martinez-Moreno, Victor M. Diaz, Marina Garcia-Peydro, Oana Hangiu, Laura Diez-Alonso, Angela Albitre, Petronila Penela, Maria L. Toribio, Pablo Menendez, Luis Alvarez-Vallina, Diego Sanchez Martinez
Summary: CD1a-STAb T cells could be an alternative to CD1a-CAR T cells for coT-ALL patients with aggressive and hyperleukocytic relapses and limited numbers of non-leukemic effector T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Physiology
Angela Albitre, Clara Reglero, Teresa Gonzalez-Munoz, Petronila Penela
Summary: Cancer progression involves complex interactions between tumor cells and the surrounding microenvironment. Chronic psychosocial stress and sympathetic nervous system activation lead to abnormal catecholamine release, impacting tumor cells directly and indirectly and fueling cancer-promoting effects. Understanding the interaction between adrenergic receptors and other signaling pathways is crucial for developing effective therapies targeting adrenergic-driven breast cancer progression.
CURRENT OPINION IN PHYSIOLOGY
(2023)
Article
Chemistry, Medicinal
Maria Neves, Cristina Perpina-Viciano, Petronila Penela, Carsten Hoffmann, Federico Mayor
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)