Article
Biochemical Research Methods
Cong Wang, Chunjing Chen, Zhenrui Pan, Yaohui He, Zhanming Zhang, Rongdiao Liu, Yuhua Xue, Qiang Zhou, Xiang Gao
Summary: Brd4 has attracted significant attention as a potential drug target due to its involvement in oncogenesis, inflammation, and HIV-1 transcription. Mass spectrometry-based quantitative proteomics identified 352 proteins that interact with CDK9, among which the increased bindings of HSP90 and CDC37 were particularly notable. The findings advance our understanding of how the HSP90-CDC37-P-TEFb complex regulates HIV-1 latency.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Microbiology
Taizhen Liang, Qiao Zhang, Ziyao Wu, Pei Chen, Yifan Huang, Shuwen Liu, Lin Li
Summary: HIV-1 latency is influenced by host factors and viral proteins, with UHRF1 playing a crucial role in modulating Tat stability. By disrupting the Tat/cyclin T1/CDK9 complex, UHRF1 suppresses HIV-1 transcription and maintains latency. This study provides new insights into controlling Tat expression through host-pathogen interaction for modulating HIV-1 latency, suggesting potential therapeutic strategies for HIV-1 patients.
Article
Biochemistry & Molecular Biology
Rongdiao Liu
Summary: CDK9 is a crucial kinase subunit of P-TEFb that is important for effective transcriptional elongation. The activity of P-TEFb is maintained through dynamic association with larger protein complexes. In this study, we find that CDK9 expression is induced upon inhibition of P-TEFb activity, a process dependent on Brd4. Inhibition of Brd4 synergizes with CDK9 inhibitor to suppress P-TEFb activity and tumor cell growth. Our findings suggest that combined inhibition of Brd4 and CDK9 could be a potential therapeutic strategy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biology
Qingqing Guan, Zhaosu Chen, Fang Yu, Lingling Liu, Yuanyong Huang, Gang Wei, Cheng-Ming Chiang, Jiemin Wong, Jiwen Li
Summary: By using a series of MYC mutants, we found that MYC can promote global transcription and enhance serine 2 phosphorylation of RNA polymerase II C-terminal domain, even when deficient in DNA binding or known transcriptional activation activities. The ability of MYC mutants to promote global transcription and serine 2 phosphorylation correlates with their ability to suppress CDK9 SUMOylation and enhance positive transcription elongation factor b (P-TEFb) complex formation. Furthermore, MYC's activity in enhancing global transcription contributes to its activity in promoting cell proliferation and transformation.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Subham Basu, Arijit Nandy, Avik Ghosh, Dheerendra Pratap Mall, Debabrata Biswas
Summary: This study reveals the important role of STUB1 in regulating the overall level of CDK9 and P-TEFb complex. STUB1 acts as a ubiquitin E3 ligase for the proteasomal degradation of CDK9. CyclinT1 protects CDK9 from STUB1-mediated degradation through binding to the same region of CDK9. Knockdown of STUB1 enhances CDK9 expression, leading to increased P-TEFb complex formation and transcriptional activation of diverse target genes.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Review
Oncology
Abel Tesfaye Anshabo, Robert Milne, Shudong Wang, Hugo Albrecht
Summary: Cyclin-dependent kinases play a crucial role in cancer development, particularly in cell division and transcription. Dysregulation of the CDK9 pathway has been observed in various hematological and solid malignancies, making it a valuable anticancer target.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Kaori Asamitsu, Takatsugu Hirokawa, Takashi Okamoto
Summary: This study identified a unique cavity structure of CDK9 induced by Tat binding and screened compounds that could inhibit CDK9 activity. It also found that one such compound showed strong inhibitory activity against CDK9 and CDK6.
Article
Multidisciplinary Sciences
Michael DeBerardine, Gregory T. Booth, Philip P. Versluis, John T. Lis
Summary: Promoter-proximal pausing by RNA Pol II is a critical aspect of transcriptional regulation in higher eukaryotes. The study shows that only NELF-mediated pausing enforces a strict early checkpoint for Cdk9, shutting down gene transcription efficiently. NELF-depleted cells in Drosophila melanogaster recapitulate the NELF-independent pausing observed in fission yeast. Importantly, only NELF-mediated pausing requires Cdk9 kinase activity for the release of paused Pol II into productive elongation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Stephin J. Vervoort, Sarah A. Welsh, Jennifer R. Devlin, Elisa Barbieri, Deborah A. Knight, Sarah Offley, Stefan Bjelosevic, Matteo Costacurta, Izabela Todorovski, Conor J. Kearney, Jarrod J. Sandow, Zheng Fan, Benjamin Blyth, Victoria McLeod, Joseph H. A. Vissers, Karolina Pavic, Ben P. Martin, Gareth Gregory, Elena Demosthenous, Magnus Zethoven, Isabella Y. Kong, Edwin D. Hawkins, Simon J. Hogg, Madison J. Kelly, Andrea Newbold, Kaylene J. Simpson, Otto Kauko, Kieran F. Harvey, Michael Ohlmeyer, Jukka Westermarck, Nathanael Gray, Alessandro Gardini, Ricky W. Johnstone
Summary: CDK9 regulates gene expression by controlling the pausing checkpoint during the transcription cycle, while PP2A counteracts CDK9-mediated phosphorylation. Loss of INTS6 leads to resistance to CDK9 inhibition-induced tumor cell death, and pharmacological activation of PP2A in combination with CDK9 inhibition provides therapeutic benefits in vivo.
Article
Multidisciplinary Sciences
Katiana Tantale, Encarnation Garcia-Oliver, Adele L'Hostis, Yueyuxio Yang, Marie-Cecile Robert, Thierry Gostan, Alja Kozulic-Pirher, Jean-Christophe Andrau, Florian Mueller, Eugenia Basyuk, Ovidiu Radulescu, Edouard Bertrand, Nikolay Tsanov, Rachel Topno, Meenakshi Basu-Shrivastava, Kamalika Mukherjee, Vera Slaninova
Summary: The study reveals that in latent HIV-1 cells, RNA polymerases undergo long-lived pausing, effectively limiting viral transcription. This pausing is stochastic rather than obligatory, with only a small fraction of polymerases experiencing long-lived pausing. The stochastic pausing leads to burst-like HIV-1 transcription in latent cells, facilitating the randomness of viral reactivation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ranadip Mandal, Monika Raab, Franz Roedel, Andrea Kraemer, Izabela Kostova, Samuel Pena-Llopis, Bjorn Haeupl, Thomas Oellerich, Khayal Gasimli, Mourad Sanhaji, Sven Becker, Klaus Strebhardt
Summary: This study identifies a new mechanism where nuclear Caspase-8 inhibits the activity of CDK9, leading to poor prognosis and chemoresistance in cervical cancer. Caspase-8-deficient cervical cancer cells show increased resistance to CDK9 inhibitors, but combination with Cisplatin can synergistically overcome this resistance.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Immunology
Silvere D. Zaongo, Yanqiu Liu, Vijay Harypursat, Fangzhou Song, Huan Xia, Ping Ma, Yaokai Chen
Summary: Antiretroviral therapy (ART) is the only currently effective method to treat HIV-1 infection, but may be toxic to vital organs. Therefore, considering HIV-1 restriction factors from the innate immune system to explore novel therapeutic approaches is seen as a promising strategy by researchers.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
James W. Bruce, Megan Bracken, Edward Evans, Nathan Sherer, Paul Ahlquist
Summary: ZBTB2, recruited to the HIV-1 promoter by ZASC1, represses transcription by interacting with cellular histone deacetylases. Activation of the ATR/DNA damage pathway, mediated by Vpr, regulates ZBTB2 relocalization and transcriptional activity, providing insights into HIV-1 gene expression regulation.
Article
Oncology
Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J. Johnson, Melanie M. Frigault, Joy M. Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C. Byrd, Rosa Lapalombella
Summary: The highly selective inhibitor VIP152 of CDK9 has shown promising results in treating chronic lymphocytic leukemia (CLL), reducing disease burden and improving overall survival rates.
Article
Microbiology
Emily Hsieh, Derek H. A. Janssens, Patrick J. E. Paddison, Edward P. A. Browne, Steve E. Henikoff, Molly A. OhAinle, Michael E. Emerman
Summary: By developing a new CRISPR screening strategy called "Latency HIV-CRISPR", we gained insights into the mechanisms controlling the latency of HIV-1. Our study found that the ING3 component of the NuA4 HAT complex acts in synergy with AZD5582 to activate latent HIV-1 proviruses. This research is important for understanding the maintenance mechanisms of HIV-1 latency.
Article
Immunology
Rajesh Ramakrishnan, Hongbing Liu, Andrew P. Rice
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2015)
Review
Microbiology
Andrew P. Rice, Jason T. Kimata
CELL HOST & MICROBE
(2015)
Article
Virology
Sona Budhiraja, Hongbing Liu, Jacob Couturier, Anna Malovannaya, Jun Qin, Dorothy E. Lewis, Andrew P. Rice
JOURNAL OF VIROLOGY
(2015)
Review
Cell Biology
Andrew P. Rice
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2015)
Article
Immunology
Md Saha Jamaluddin, Pei-Wen Hu, Yih Jan, Edward B. Siwak, Andrew P. Rice
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2016)
Review
Immunology
Jason T. Kimata, Andrew P. Rice, Jin Wang
CURRENT OPINION IN IMMUNOLOGY
(2016)
Review
Pharmacology & Pharmacy
Andrew P. Rice
EXPERT OPINION ON THERAPEUTIC TARGETS
(2016)
Article
Biochemical Research Methods
Philipp Kaiser, Sunil K. Joshi, Peggy Kim, Peilin Li, Hongbing Liu, Andrew P. Rice, Joseph K. Wong, Steven A. Yukl
JOURNAL OF VIROLOGICAL METHODS
(2017)
Article
Biochemistry & Molecular Biology
Zheng Zhang, Bryan C. Nikolai, Leah A. Gates, Sung Yun Jung, Edward B. Siwak, Bin He, Andrew P. Rice, Bert W. O'Malley, Qin Feng
NUCLEIC ACIDS RESEARCH
(2017)
Article
Immunology
Jamaluddin Md Saha, Hongbing Liu, Pei-Wen Hu, Bryan C. Nikolai, Hulin Wu, Hongyu Miao, Andrew P. Rice
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2018)
Review
Virology
Sona Budhiraja, Andrew P. Rice
Article
Virology
Berenice Carrillo, Jae-Mun Choi, Zachary A. Bornholdt, Banumathi Sankaran, Andrew P. Rice, B. V. Venkataram Prasad
JOURNAL OF VIROLOGY
(2014)
Article
Virology
Karen Chiang, Hongbing Liu, Andrew P. Rice
Article
Biochemical Research Methods
Shupeng Gui, Andrew P. Rice, Rui Chen, Liang Wu, Ji Liu, Hongyu Miao
BMC BIOINFORMATICS
(2017)
Review
Pharmacology & Pharmacy
Andrew P. Rice
CURRENT PHARMACEUTICAL DESIGN
(2017)