Anniina Vihervaara
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Assistant Professor at KTH Royal Institute of Technology
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About
Anniina Vihervaara is an Assistant Professor at KTH Royal Institute of Technology in Sweden. Her research primarily focuses on transcriptional regulation, RNA synthesis, and molecular modifications of RNA polymerase II complexes, as evidenced by her recent publications. She is involved in exploring the impact of various compounds on RNA synthesis and cancer cell behavior, contributing to the understanding of gene regulation in stress and disease contexts.
Recent Grants
Grant: Open
Science for Life Lab Fellow
Open Date: 2020-12-01
Close Date: 2026-11-01
Grant: Close
Academy of Finland Postdoctoral Researcher
Open Date: 2019-09-01
Close Date: 2022-08-01
Articles (6)
Inhibition of CDK12 elevates cancer cell dependence on P-TEFb by stimulation of RNA polymerase II pause release
P-TEFb and CDK12 facilitate transcriptional elongation by RNA polymerase II. Given the prominence of both kinases in cancer, gaining a better understanding of their interplay could inform the design of novel anti-cancer strategies. While down-regulation of DNA repair genes in CDK12-targeted cancer cells is being explored therapeutically, little is known about mechanisms and significance of transcriptional induction upon inhibition of CDK12. We show that selective targeting of CDK12 in colon cancer-derived cells activates P-TEFb via its release from the inhibitory 7SK snRNP. In turn, P-TEFb stimulates Pol II pause release at thousands of genes, most of which become newly dependent on P-TEFb. Amongst the induced genes are those stimulated by hallmark pathways in cancer, including p53 and NF-κB. Consequently, CDK12-inhibited cancer cells exhibit hypersensitivity to inhibitors of P-TEFb. While blocking P-TEFb triggers their apoptosis in a p53-dependent manner, it impedes cell proliferation irrespective of p53 by preventing induction of genes downstream of the DNA damage-induced NF-κB signaling. In summary, stimulation of Pol II pause release at the signal-responsive genes underlies the functional dependence of CDK12-inhibited cancer cells on P-TEFb. Our study establishes the mechanistic underpinning for combinatorial targeting of CDK12 with either P-TEFb or the induced oncogenic pathways in cancer.
Year:
2023
Collaborators (8)
zhijia wang
University of Helsinki
Maria Vartiainen
University of Helsinki
Lea Sistonen
Åbo Akademi University
John Lis
Barbara McClintock Professor of Molecular Biology and Genetics
Cornell University
Bina Prajapati
University of Helsinki
Rocio Gomez-Pastor
Assistant Professor
University of Minnesota
Maria Sokolova
University of Helsinki
Matjaž Barborič
University of Helsinki

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