Targeting transcription cycles in cancer

SJ Vervoort, JR Devlin, N Kwiatkowski, M Teng… - Nature Reviews …, 2022 - nature.com
Accurate control of gene expression is essential for normal development and dysregulation
of transcription underpins cancer onset and progression. Similar to cell cycle regulation …

Pre-mRNA splicing and its cotranscriptional connections

H Shenasa, DL Bentley - Trends in Genetics, 2023 - cell.com
Transcription of eukaryotic genes by RNA polymerase II (Pol II) yields RNA precursors
containing introns that must be spliced out and the flanking exons ligated together. Splicing …

An atlas of substrate specificities for the human serine/threonine kinome

JL Johnson, TM Yaron, EM Huntsman, A Kerelsky… - Nature, 2023 - nature.com
Protein phosphorylation is one of the most widespread post-translational modifications in
biology,. With advances in mass-spectrometry-based phosphoproteomics, 90,000 sites of …

[HTML][HTML] CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release

T Velychko, E Mohammad, I Ferrer-Vicens, I Parfentev… - Molecular Cell, 2024 - cell.com
Summary Cyclin-dependent kinase 7 (CDK7), part of the general transcription factor TFIIH,
promotes gene transcription by phosphorylating the C-terminal domain of RNA polymerase …

SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape

S Hu, L Peng, C Xu, Z Wang, A Song, FX Chen - Molecular Cell, 2021 - cell.com
Transcription progression is governed by multitasking regulators including SPT5, an
evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer …

Oncogenic CDK13 mutations impede nuclear RNA surveillance

ML Insco, BJ Abraham, SJ Dubbury, IH Kaltheuner… - Science, 2023 - science.org
RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity.
We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase …

From structure modification to drug launch: A systematic review of the ongoing development of cyclin-dependent kinase inhibitors for multiple cancer therapy

Z Shi, L Tian, T Qiang, J Li, Y **ng, X Ren… - Journal of medicinal …, 2022 - ACS Publications
Herein, we discuss more than 50 cyclin-dependent kinase (CDK) inhibitors that have been
approved or have undergone clinical trials and their therapeutic application in multiple …

Transcription associated cyclin-dependent kinases as therapeutic targets for prostate cancer

TA Constantin, KK Greenland, A Varela-Carver… - Oncogene, 2022 - nature.com
Transcriptional deregulation has emerged as a hallmark of several cancer types. In
metastatic castration-resistant prostate cancer, a stage in which systemic androgen …

Discovery of SY-5609: a selective, noncovalent inhibitor of CDK7

JJ Marineau, KB Hamman, S Hu… - Journal of Medicinal …, 2021 - ACS Publications
CDK7 has emerged as an exciting target in oncology due to its roles in two important
processes that are misregulated in cancer cells: cell cycle and transcription. This report …

Cyclin‐dependent kinases: Masters of the eukaryotic universe

AJ Pluta, C Studniarek, S Murphy… - Wiley Interdisciplinary …, 2024 - Wiley Online Library
A family of structurally related cyclin‐dependent protein kinases (CDKs) drives many
aspects of eukaryotic cell function. Much of the literature in this area has considered …