Article
Cell Biology
Badri Krishnan, Takaaki Yasuhara, Purva Rumde, Marcello Stanzione, Chenyue Lu, Hanjun Lee, Michael S. Lawrence, Lee Zou, Linda T. Nieman, Ioannis Sanidas, Nicholas J. Dyson
Summary: RB restricts G1/S progression by inhibiting E2F, but also affects chromosome architecture and cellular state. Expression of RB and G1 arrest leads to visible changes in chromosome structure, which are related to RB activity, specific isoforms of monophosphorylated RB, and known RB-associated activities. Delt ΔCK-RB alters physical interactions between genomic loci, but these changes are not affected by dominant-negative DN.
JOURNAL OF CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kurt Engeland
Summary: RB and p53 are central tumor suppressors that play key roles in regulating the cell division cycle. RB downregulates numerous genes by forming complexes with E2F transcription factors, and its repression is released through phosphorylation. p53 activates CDKN1A gene to regulate RB phosphorylation, leading to expression of cell cycle regulators. There is an overlap between RB and DREAM signaling pathways.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Alberta Palazzo, Hector Hernandez-Vargas, Delphine Goehrig, Jean-Jacques Medard, David Vindrieux, Jean-Michel Flaman, David Bernard
Summary: Cancer cells arising from senescent cells display more aggressive features and resistance to drugs. A molecular signature of these cells can serve as a prognostic marker for several human cancers.
Article
Oncology
Amy C. Mandigo, Ayesha A. Shafi, Jennifer J. McCann, Wei Yuan, Talya S. Laufer, Denisa Bogdan, Lewis Gallagher, Emanuela Dylgjeri, Galina Semenova, Irina A. Vasilevskaya, Matthew J. Schiewer, Chris M. McNair, Johann S. de Bono, Karen E. Knudsen
Summary: This study reveals that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease.
Article
Cell Biology
Alexandra E. Rader, Battuya Bayarmagnai, Maxim V. Frolov
Summary: The RB and Hippo pathways interact to regulate cell proliferation and differentiation. When these pathways are inactivated, photoreceptor cells lose their neuronal identity and dedifferentiate into a progenitor-like fate. Inappropriate activation of the retinal differentiation suppressor hth by Yki/Sd is responsible for this dedifferentiation process.
DEVELOPMENTAL CELL
(2023)
Review
Microbiology
Boris Bogdanow, Quang Vinh Phan, Luder Wiebusch
Summary: Cytomegaloviruses induce significant changes in cell cycle regulation to enable replication of their DNA genomes. They establish a unique cell cycle arrest at the G(1)/S transition, while activating S phase-specific gene expression and nucleotide metabolism. Despite similarities in cell cycle regulation between human and murine CMVs, there are considerable differences in viral cell cycle effectors and mechanisms of action.
Article
Oncology
Amy C. Mandigo, Wei Yuan, Kexin Xu, Peter Gallagher, Angel Pang, Yi Fang Guan, Ayesha A. Shafi, Chellappagounder Thangavel, Beshara Sheehan, Denisa Bogdan, Alec Paschalis, Jennifer J. McCann, Talya S. Laufer, Nicolas Gordon, Irina A. Vasilevskaya, Emanuela Dylgjeri, Saswati N. Chand, Matthew J. Schiewer, Josep Domingo-Domenech, Robert B. Den, Jeff Holst, Peter A. McCue, Johann S. de Bono, Christopher McNair, Karen E. Knudsen
Summary: This study identifies the stage-specific consequences of RB loss across cancer progression, which directly impact tumor response to clinically utilized therapeutics. It is the first to investigate the effect of RB loss on global metabolic regulation and link RB/E2F1 to redox control in multiple advanced diseases.
Article
Biochemistry & Molecular Biology
Ioannis Sanidas, Hanjun Lee, Purva H. Rumde, Gaylor Boulay, Robert Morris, Gabriel Golczer, Hanjun Gaylor Boulay, Marcelo Stanzione, Soroush Hajizadeh, Jun Zhong, Meagan B. Ryan, Ryan B. Corcoran, Benjamin J. Drapkin, Miguel N. Rivera, Nicholas J. Dyson, Michael S. Lawrence
Summary: The interaction between RB and chromatin is crucial for understanding its molecular functions. This study reveals that RB binds not only to promoters, but also to enhancers and insulators. The distribution of RB in the cell cycle differs, with enrichment at promoters in G1 and non-promoter sites in cycling cells. RB-bound promoters are consistent across lineages, while RB-bound enhancers vary between cell types and associate with different categories of genes.
Article
Medicine, Research & Experimental
Yuntan Qiu, Meng Meng, Chuanzhen Cao, Jingyuan Zhang, Xu Cheng, Yongxin Huang, Haotian Cao, Yun Li, Duanqing Tian, Yongsheng Huang, Li Peng, Kaishun Hu, Yin Zhang, Jianyou Liao, Jiehua He, Xiaochun Wang, Daning Lu, Lehang Lin, Xingang Bi, Dong Yin
Summary: MEX3A is an RNA-binding protein that promotes mRNA decay through binding to 30 untranslated regions. This study reveals that MEX3A is upregulated in clear cell renal cell carcinoma and its transcription is activated by ETS1. Silencing MEX3A reduces cell proliferation and induces G1/S cell-cycle arrest. Gene set enrichment analysis identified E2F targets as the central downstream pathways of MEX3A. Further assays demonstrated that MEX3A binds to the CDKN2B 30 untranslated region, promoting its mRNA degradation and leading to uncontrolled cell cycle in clear cell renal cell carcinoma.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Sivasankar Putta, Lucia Alvarez, Stephan Luedtke, Peter Sehr, Gerd A. Muller, Samantha M. Fernandez, Sarvind Tripathi, Joe Lewis, Toby J. Gibson, Lucia B. Chemes, Seth M. Rubin
Summary: The retinoblastoma protein (Rb) and its homologs p107 and p130 play critical roles in regulating gene expression during the cell cycle and are frequently inactivated in cancer. This study presents binding data and crystal structures of the p107 pocket domain in complex with LxCxE peptides from transcriptional co-repressor proteins, providing new insights into how Rb proteins bind their cell partners with varying affinity and specificity.
Article
Biology
Luis Gregory Zamalloa, Margaret M. Pruitt, Nicole M. Hermance, Himabindu Gali, Rachel L. Flynn, Amity L. Manning
Summary: This study investigates the impact of RB dysfunction on genome stability and whether this change can be exploited in RB-deficient cancer cells. The findings demonstrate that RB loss leads to high levels of PARylation, and inhibiting PARylation allows RB-deficient cells to progress to mitosis despite replication stress. These defects result in high levels of DNA damage and compromised cell viability. Therefore, drugs targeting PARP1 and PARP2 may have clinical relevance in the treatment of RB-deficient cancers.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Yashika Agrawal, Tanisha Sharma, Sehbanul Islam, Kaustubh S. Nadkarni, Manas Kumar Santra
Summary: This study reveals the role of FBXO41 in cancer progression, demonstrating its ability to suppress cancer cell proliferation and tumor growth by inducing autophagic cell death through an alternative pathway. It establishes a new FBXO41-SKP2-p21 axis for induction of autophagic cell death to prevent cancer growth, providing a potential avenue for the development of promising cancer therapeutics.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Oncology
Brian M. Olson, Kiranj Chaudagar, Riyue Bao, Sweta Sharma Saha, Christina Hong, Marguerite Li, Srikrishnan Rameshbabu, Raymond Chen, Alison Thomas, Akash Patnaik
Summary: Retinoblastoma loss-of-function (LOF) can lead to non-T-cell-inflamed immunologically cold tumor microenvironments, reducing the responsiveness to immune checkpoint blockade. Inhibiting BET domain and extraterminal (BET) protein can reprogram the tumor microenvironment, increasing T-cell infiltration and enhancing the sensitivity of Rb-deficient prostate cancer to immune checkpoint blockade.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Physiology
Tianyu He, Xiaoyun Zhang, Jianyu Hao, Shigang Ding
Summary: The PTEN gene is a crucial tumor suppressor gene with diverse biological functions, playing important roles in cell morphology, proliferation, differentiation, and other processes. While well-documented in malignant tumors of the digestive system, PTEN may also be involved in benign processes and non-neoplastic diseases of the digestive tract. Recent discoveries of PTEN isoforms hold promise for understanding its broader biological effects in non-neoplastic digestive diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Oncology
Varadha Balaji Venkadakrishnan, Yasutaka Yamada, Kenny Weng, Osasenaga Idahor, Himisha Beltran
Summary: Cancer cells can change their phenotype in response to environmental stimuli or therapy, a phenomenon known as phenotypic plasticity. This plasticity is often associated with loss of dependence on the original oncogenic driver and is influenced by underlying genetic and epigenetic alterations. Understanding the molecular drivers of cancer plasticity is crucial for developing new therapeutic strategies. RB gene loss plays a vital role in unlocking cancer phenotypic plasticity and driving therapy resistance across various types of cancer. It is important to explore therapeutic approaches targeting RB loss in cancers undergoing lineage reprogramming.
MOLECULAR CANCER RESEARCH
(2023)
Article
Cell Biology
Yufeng Lu, Fion Shiau, Wenyang Yi, Suying Lu, Qian Wu, Joel D. Pearson, Alyssa Kallman, Suijuan Zhong, Thanh Hoang, Zhentao Zuo, Fangqi Zhao, Mei Zhang, Nicole Tsai, Yan Zhuo, Sheng He, Jun Zhang, Genevieve L. Stein-O'Brien, Thomas D. Sherman, Xin Duan, Elana J. Fertig, Loyal A. Goff, Donald J. Zack, James T. Handa, Tian Xue, Rod Bremner, Seth Blackshaw, Xiaoqun Wang, Brian S. Clark
DEVELOPMENTAL CELL
(2020)
Article
Medicine, Research & Experimental
Jason Charish, Alireza P. Shabanzadeh, Danian Chen, Patrick Mehlen, Santhosh Sethuramanujam, Hidekiyo Harada, Vera L. Bonilha, Gautam Awatramani, Rod Bremner, Philippe P. Monnier
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Evan Amalfitano, Margot Karlikow, Masoud Norouzi, Katariina Jaenes, Seray Cicek, Fahim Masum, Peivand Sadat Mousavi, Yuxiu Guo, Laura Tang, Andrew Sydor, Duo Ma, Joel D. Pearson, Daniel Trcka, Mathieu Pinette, Aruna Ambagala, Shawn Babiuk, Bradley Pickering, Jeff Wrana, Rod Bremner, Tony Mazzulli, David Sinton, John H. Brumell, Alexander A. Green, Keith Pardee
Summary: The combination of gene circuit-based sensors with a glucose meter has enabled small molecule analyte and nucleic acid detection. This technology has potential applications in various fields, including infectious disease detection and potential pandemic response.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Marie-Ming Aynaud, J. Javier Hernandez, Seda Barutcu, Ulrich Braunschweig, Kin Chan, Joel D. Pearson, Daniel Trcka, Suzanna L. Prosser, Jaeyoun Kim, Miriam Barrios-Rodiles, Mark Jen, Siyuan Song, Jess Shen, Christine Bruce, Bryn Hazlett, Susan Poutanen, Liliana Attisano, Rod Bremner, Benjamin J. Blencowe, Tony Mazzulli, Hong Han, Laurence Pelletier, Jeffrey L. Wrana
Summary: The study introduces a platform called C19-SPAR-Seq, which can analyze tens of thousands of patient samples for SARS-CoV-2 in a single run, with high specificity and sensitivity demonstrated through experimental trials in clinical diagnostics.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Joel D. Pearson, Daniel Trcka, Suying Lu, Sharon J. Hyduk, Mark Jen, Marie-Ming Aynaud, J. Javier Hernandez, Philippos Peidis, Miriam Barrios-Rodiles, Kin Chan, Jim Woodgett, Tony Mazzulli, Liliana Attisano, Laurence Pelletier, Myron I. Cybulsky, Jeffrey L. Wrana, Rod Bremner
Summary: The study evaluated the use of direct RT-qPCR and indirect methods with RNA extraction in COVID-19 testing. Results showed that the BGI system outperformed other systems in performance but at a higher cost, while the Norgen system was able to accurately detect samples with clinical Ct < 33 and save costs.
Article
Oncology
Joel D. Pearson, Katherine Huang, Marek Pacal, Sean R. McCurdy, Suying Lu, Arthur Aubry, Tao Yu, Kristine M. Wadosky, Letian Zhang, Tao Wang, Alex Gregorieff, Mohammad Ahmad, Helen Dimaras, Ellen Langille, Susan P. C. Cole, Philippe P. Monnier, Benjamin H. Lok, Ming-Sound Tsao, Nagako Akeno, Daniel Schramek, Kathryn A. Wikenheiser-Brokamp, Erik S. Knudsen, Agnieszka K. Witkiewicz, Jeffrey L. Wrana, David W. Goodrich, Rod Bremner
Summary: The study identifies two binary cancer classes based on the activity of YAP, providing insights into the impact of cancer heterogeneity on therapeutic response. YAP silencing is intrinsic to the cell of origin and may be acquired with lineage switching and drug resistance.
Article
Biochemistry & Molecular Biology
Arturo Ortin-Martinez, Nicole E. Yan, En Leh Samuel Tsai, Lacrimioara Comanita, Akshay Gurdita, Nobuhiko Tachibana, Zhongda C. Liu, Suying Lu, Parnian Dolati, Neno T. Pokrajac, Ahmed El-Sehemy, Philip E. B. Nickerson, Carol Schuurmans, Rod Bremner, Valerie A. Wallace
Summary: Recent studies have demonstrated that intracellular molecules and organelles can transfer between cells during embryonic development, tissue homeostasis and disease. Through cell transplantation, researchers have observed bidirectional transfer of intracellular material between transplanted and host cells, revealing a process termed material transfer (MT) that requires cell contact and stable microtubule-containing protrusions. Targeting actin remodeling inhibits MT, suggesting a mechanism for horizontal exchange of intracellular material via nanotube-like connections between neurons in vivo.
Article
Multidisciplinary Sciences
Akshay Gurdita, Philip E. B. Nickerson, Neno T. Pokrajac, Arturo Ortin-Martinez, En Leh Samuel Tsai, Lacrimioara Comanita, Nicole E. Yan, Parnian Dolati, Nobuhiko Tachibana, Zhongda C. Liu, Joel D. Pearson, Danian Chen, Rod Bremner, Valerie A. Wallace
Summary: The study developed an optimized tissue clearing and depigmentation protocol called InVision for whole-eye fluorescent marker tissue imaging, allowing analysis of various eye biological processes such as retinal architecture, immunostaining, 3D volumetric analysis, and protein exchange. This method can provide novel insights into the local cellular networks involved in cell biological processes in the eye.
Article
Oncology
Safa Majeed, Mansi K. Aparnathi, Kevin C. J. Nixon, Vidhyasagar Venkatasubramanian, Fariha Rahman, Lifang Song, Jessica Weiss, Ranya Barayan, Vijithan Sugumar, Samir H. Barghout, Joel D. Pearson, Rod Bremner, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, Benjamin H. Lok
Summary: TAK-243 exhibits efficacy in preclinical models of small cell lung cancer (SCLC), with associations to various gene sets. TAK-243 synergizes with cisplatin/etoposide chemotherapy (C/E) and PARP inhibitor olaparib. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Zhe Jiang, Huiqin Li, Stephanie A. Schroer, Veronique Voisin, Youngjun Ju, Marek Pacal, Natalie Erdmann, Wei Shi, Philip E. D. Chung, Tao Deng, Nien-Jung Chen, Giovanni Ciavarra, Alessandro Datti, Tak W. Mak, Lea Harrington, Frederick A. Dick, Gary D. Bader, Rod Bremner, Minna Woo, Eldad Zacksenhaus
Summary: By knocking out phosphorylation sites of pRb in mice, researchers found that this modification does not affect embryonic and early development, but leads to premature aging phenotypes such as infertility, kyphosis, and diabetes. These results have important implications for cell cycle regulation, diabetes treatment, and longevity research.
Article
Multidisciplinary Sciences
Suying Lu, David Duplat, Paula Benitez-Bolivar, Cielo Leon, Stephany D. Villota, Eliana Veloz-Villavicencio, Valentina Arevalo, Katariina Jaenes, Yuxiu Guo, Seray Cicek, Lucas Robinson, Philippos Peidis, Joel D. Pearson, Jim Woodgett, Tony Mazzulli, Patricio Ponce, Silvia Restrepo, John M. Gonzalez, Adriana Bernal, Marcela Guevara-Suarez, Keith Pardee, Varsovia E. Cevallos, Camila Gonzalez, Rod Bremner
Summary: Continued waves, new variants, and limited vaccine deployment underline the importance of SARS-CoV-2 tests in controlling the COVID-19 pandemic. This study optimized the RT-LAMP method for testing in low/medium resource settings and found it to be as sensitive as RT-PCR in detecting SARS-CoV-2. The study also demonstrated the effectiveness of a portable PoC device in replacing traditional thermocyclers for testing.
Article
Cell Biology
Erik S. Knudsen, Vishnu Kumarasamy, Ram Nambiar, Joel D. Pearson, Paris Vail, Hanna Rosenheck, Jianxin Wang, Kevin Eng, Rod Bremner, Daniel Schramek, Seth M. Rubin, Alana L. Welm, Agnieszka K. Witkiewicz
Summary: Progression through G1/S phase of the cell cycle is regulated by different CDK activities and cyclins, with varying requirements depending on tumor origin and genetic alterations. RB-deficient models are intrinsically CDK4/6 independent but exhibit different dependencies on cyclin E. In contrast, RB-proficient models have multiple CDK4/6-independent mechanisms for G1/S progression, leading to resistance to FDA-approved inhibitors. Mining therapeutic sensitivities reveals reciprocal vulnerabilities associated with RB1 or CCND1 expression versus CCNE1 or CDKN2A.
Article
Biology
Yimeng Fan, Wenyue Chen, Ran Wei, Wei Qiang, Joel D. Pearson, Tao Yu, Rod Bremner, Danian Chen
Summary: The study precisely mapped the insertion site of the Pax6-alpha-Cre transgene and found unexpected expression in olfactory neurons. The results indicate that the commonly used mouse line for retinal studies has transgene insertion within gene clusters of olfactory and vomeronasal receptors, leading to expression in not just retinal, but also olfactory and vomeronasal sensory neurons.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Arthur Aubry, Joel D. Pearson, Jason Charish, Tao Yu, Jeremy M. Sivak, Dimitris P. Xirodimas, Herve Avet-Loiseau, Jill Corre, Philippe P. Monnier, Rod Bremner
Summary: The neddylation inhibitor MLN4924/Pevonedistat is under clinical trials for various types of cancers. It shows efficacy by inhibiting multiple cellular networks and synergizing with standard-of-care drugs, potentially providing a broad therapeutic relevance.
Article
Biochemical Research Methods
Joel D. Pearson, Rod Bremner
Summary: Ectopic/overexpression systems are crucial for studying protein function, but precautions must be taken to prevent artifacts caused by excessively high levels of overexpression. A lentiviral system has been developed to ectopically express YAP/TAZ at physiologically relevant levels for studying their function in YAP/TAZ-deficient cancers. This system can be easily adapted for studying other proteins and expression levels can be assessed using flow cytometry and quantitative western blotting.
