NUAK kinases: Signaling mechanisms and therapeutic applications

Authors

Nicole M. Cullen, Tulane University School of Medicine, New Orleans, LA
Peter Rosston, University of North Carolina at Chapel Hill, Chapel Hill, NC
Bakhtawar Tufail, Tulane University School of Medicine, New Orleans, LA
Anne E. D'Armond, Tulane University School of Medicine, New Orleans, LA
Ayushi Patel, LSU Health Sciences Center - New OrleansFollow
Dara H. Khosravi, LSU Health Sciences Center - New OrleansFollow
Bridgette M. Collins-Burow, Tulane University School of Medicine, New Orleans, LA
Van T. Hoang, Tulane University School of Medicine, New Orleans, LA
Elizabeth C. Martin, Tulane University School of Medicine, New Orleans, LA
David H. Drewry, University of North Carolina at Chapel Hill, Chapel Hill, NC
Matthew E. Burow, Tulane University School of Medicine, New Orleans, LA
Suresh K. Alahari, LSU Health Sciences Center - New OrleansFollow

Document Type

Article

Publication Date

8-5-2025

Publication Title

Journal of Biological Chemistry

Abstract

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate the biological roles and signaling pathways of the NUAK kinases in a range of malignancies, focusing on cancer but also covering noncancerous physiology, and the therapeutic potential of NUAK kinase inhibition. We summarize the known small-molecule NUAK kinase inhibitors in preclinical models and one inhibitor in clinical trials. This review highlights the signaling mechanisms and therapeutic value of targeting NUAK kinase signaling pathways with specific, small-molecule NUAK inhibitors.

PubMed ID

40774384

Volume

301

Issue

9

Publisher

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Cullen, Nicole M.; Rosston, Peter; Tufail, Bakhtawar; D'Armond, Anne E.; Patel, Ayushi; Khosravi, Dara H.; Collins-Burow, Bridgette M.; Hoang, Van T.; Martin, Elizabeth C.; Drewry, David H.; Burow, Matthew E.; and Alahari, Suresh K., "NUAK kinases: Signaling mechanisms and therapeutic applications" (2025). School of Medicine Faculty Publications. 4013.
https://digitalscholar.lsuhsc.edu/som_facpubs/4013
10.1016/j.jbc.2025.110565