Review
Biochemistry & Molecular Biology
Valerio Nardone, Marcella Barbarino, Antonio Angrisani, Pierpaolo Correale, Pierpaolo Pastina, Salvatore Cappabianca, Alfonso Reginelli, Luciano Mutti, Clelia Miracco, Rocco Giannicola, Antonio Giordano, Luigi Pirtoli
Summary: The expanding clinical application of CDK4- and CDK6-inhibiting drugs in breast cancer has sparked interest in testing them in other tumors. Potential combinations with other therapeutic approaches are being explored, with some hypotheses about integrating CDK4 and CDK6 inhibitors with radiotherapy. However, more research is needed to further investigate the potential benefits of these combinations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Milosz Rolinski, Nicola Pietro Montaldo, Merdane Ezgi Aksu, Sarah L. Fordyce Martin, Alessandro Brambilla, Nicolas Kunath, Jostein Johansen, Sten Even Erlandsen, Nina-Beate Liabbak, Kristin Rian, Magnar Bjoras, Pal Saetrom, Barbara van Loon
Summary: The research identified a novel mechanism of alkylation stress response dependent on MED13 and cyclin D1, which can serve as a basis for developing innovative therapeutic strategies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Min Chen, Xue Yang, Haiyang Liu, Jun Wan
Summary: In this study, a functional bipartite nuclear localization signal (bNLS) in the ANKRD11 gene was identified. It was found that this bNLS is responsible for the nuclear import of ANKRD11 and certain clinical variants of this signal may be related to disease development.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Natalia Elisa Bernardes, Ho Yee Joyce Fung, Yang Li, Zhe Chen, Yuh Min Chook
Summary: IMPORTIN-4, as the primary nuclear import receptor of core histones H3 and H4, binds the H3-H4 dimer and histone chaperone ASF1 prior to nuclear import. Through a 3.5-angstrom cryo-EM structure, the full nuclear import complex and the release process of H3-H4 in the cytoplasm and nucleus are revealed.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Nicole Brighi, Vincenza Conteduca, Cristian Lolli, Giorgia Gurioli, Giuseppe Schepisi, Michela Palleschi, Marita Mariotti, Chiara Casadei, Ugo De Giorgi
Summary: This paper reviews the expanding treatment options for prostate cancer patients, focusing on the potential therapeutic target of the cyclin-dependent kinases (CDK) pathway and the investigation of CDK4/6 inhibitors in clinical trials. The biological rationale and clinical trials for the use of CDK inhibitors in prostate cancer are discussed, along with the potential application of precision oncology in treatment selection.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Lihong He, Wei Shao, Jiang Li, Fei Deng, Hualin Wang, Zhihong Hu, Manli Wang
Summary: This study systematically analyzed the nuclear localization of 154 ORFs encoded by AcMNPV, with 25 viral proteins found to be localized in the nucleus in the absence of virus infection. Upon virus infection, 11 proteins originally located in the cytoplasm were completely translocated into the nucleus, suggesting their nuclear import is facilitated by other viral or host proteins. Further experiments identified specific proteins that were imported into the nucleus with the assistance of other nuclear localization proteins.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Immunology
Li-Li An, Xiang Zhao, Xiu-Ying Gong, Yi-Lin Li, Zi-Ling Qu, Hao-Yu Sun, Wen-Hao Guo, Cheng Dan, Jian-Fang Gui, Yi-Bing Zhang
Summary: The study reveals the regulatory roles of zebrafish IRF family members in interferon response, which are influenced by their subcellular localization and promoter binding. Zebrafish IRF family members display three distinctive patterns of constitutive localization and can act as activators or repressors of interferon gene transcription.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J. F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica
Summary: TDP-43 protein interacts with eIF5A(Hyp)(K50), and this interaction is enhanced under stress conditions. Decreasing hypusination or mutating lysine residues reduces abnormal levels of TDP-43. Importins KPNA1/2, KPNB1, and RanGTP were also identified as interacting partners of eIF5A(Hyp)(K50).
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Joshua W. Thompson, Maria F. Valdes Michel, Bryan T. Phillips
Summary: The study reveals the role of microtubule motor dynein in maintaining the centrosomal enrichment of SYS-1 and its importance in cell fate decisions in Caenorhabditis elegans. Retrograde microtubule-mediated trafficking enables SYS-1 enrichment at centrosomes, contributing to its eventual proteasomal degradation. Dysregulation of this process can lead to cell fate misspecifications.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Virology
Nhan L. T. Nguyen, Wei Wu, Nelly Pante
Summary: This study investigates the role of the nucleoprotein (NP) localization signals in the nuclear import of viral ribonucleoprotein complexes (vRNPs) during influenza A virus infection. The study demonstrates that both NLS1 and NLS2 of the NP protein are crucial for successful infection, indicating their important role in the infection cycle of the virus.
Article
Cell Biology
Helen Hoffmeister, Simon Holzinger, Marie-Sofie Duerr, Astrid Bruckmann, Susanne Schindler, Regina Groebner-Ferreira, Reinhard Depping, Gernot Laengst
Summary: Chromatin remodeling enzymes are essential for genome regulation, and the nuclear import of the human CHD4 protein is characterized in this study. It is shown that CHD4 enters the nucleus through importin-alpha proteins (1, 5, 6 and 7) independently of importin beta 1. Importin alpha 1 directly interacts with a specific motif in CHD4, but mutating this motif only leads to a partial reduction in nuclear localization, suggesting the existence of additional import mechanisms. Furthermore, CHD4 is associated with NuRD core subunits in the cytoplasm, indicating assembly of the NuRD complex before nuclear import. We propose that CHD4 is dragged into the nucleus through a 'piggyback' mechanism using the import signals of the associated NuRD subunits.
JOURNAL OF CELL SCIENCE
(2023)
Article
Oncology
Nina Nguyen, Sana Chaudhry, Tulasigeri M. Totiger, Robert Diaz, Evan Roberts, Skye Montoya, Gabriel Pardo, Alejandro Pardo, Jumana Afaghani, Maurizio Affer, Jacob Jahn, Terrence Bradley, Francesco Maura, Dickran Kazandjian, Daniel Bilbao, Jennifer Chapman, Ola Landgren, James Hoffman, Justin Taylor
Summary: In this study, the safety and therapeutic effects of simultaneous administration of venetoclax and selinexor in patients with t(11;14) multiple myeloma were reported. The combination showed synergistic effects in t(11;14) multiple myeloma cell lines and resulted in decreased levels of Cyclin D1. These findings suggest that the combination of venetoclax and selinexor may be a promising approach for the treatment of multiple myeloma.
NPJ PRECISION ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yanhui Song, Hongguang Zhang, Yinmiao Wang, Jin Guo, Shengjie Tang, Lu Wang, Ke Peng, Chun-sheng Dong
Summary: The study confirmed that KPNA2 is an important adaptor protein of the KPNB1-Pom121 pathway, mediating the nuclear transportation of HIV-1 pre-integration complex (PIC). This pathway may be a potential target for antiviral treatment against HIV-1.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Shiho Hisaoka, Jin Osawa, Riku Kobashi, Atsuhiko Ishida, Isamu Kameshita, Noriyuki Sueyoshi
Summary: Research has shown that BMP2-inducible kinase (BMP2K) forms liquid-liquid phase separated droplets in the cytoplasm, regulated by a glutamine-rich area and hyperosmolarity. The cytoplasmic localization of BMP2K is managed through the inhibition of nuclear localization signal (NLS) function via phosphorylation of Ser-1010 and the antagonism of the NLS by a newly discovered cytoplasmic localization region. These findings provide a biochemical foundation for the advancement of BMP2K-related cell biology, structural biology, and pathophysiology.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Yilin Fan, Tobias Meyer
Summary: Cell density and mitogen signals compete to regulate the levels of cyclin D1 and p27, determining whether cells proliferate or enter quiescence. The history of competing signals experienced by mother cells is funneled into a precise activator-inhibitor balance that controls the fate of daughter cells.