NUAK1

{{Short description|Protein-coding gene in the species Homo sapiens}}

NUAK family SNF1-like kinase 1 also known as AMPK-related protein kinase 5 (ARK5) is an enzyme that in humans is encoded by the NUAK1 gene.{{cite journal |vauthors=Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H | title = Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein | journal = J Biol Chem | volume = 278 | issue = 1 | pages = 48–53 |date=Dec 2002 | pmid = 12409306 | doi = 10.1074/jbc.M206025200 | s2cid = 23605132 | url = http://espace.library.uq.edu.au/view/UQ:65358/UQ65358_OA.pdf | doi-access = free }}{{cite journal |vauthors=Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Esumi H | title = ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation | journal = Oncogene | volume = 22 | issue = 40 | pages = 6177–82 |date=Sep 2003 | pmid = 13679856 | doi = 10.1038/sj.onc.1206899 | doi-access = | s2cid = 20975883 }}{{cite web | title = Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9891}}

Function

Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex.{{cite web|access-date=2021-12-19

|author=Protein Coding

|date=2021-11-14

|title=NUAK1 Gene - NUAK Family Kinase 1

|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUAK1

|website=Gene Cards

|language=en}}

Clinical significance

ARK5 is important in tumor malignancy and invasiveness.{{cite journal |vauthors=Suzuki A, Lu J, Kusakai G |title=ARK5 is a tumor invasion-associated factor downstream of Akt signaling. |journal=Mol. Cell. Biol. |volume=24 |issue= 8 |pages= 3526–35 |year= 2004 |pmid= 15060171 |doi=10.1128/MCB.24.8.3526-3535.2004 | pmc=381626 |display-authors=etal}}

Research findings

ARK5 is often overexpressed in multiple myeloma cell lines.[http://www.medpagetoday.com/clinical-context/MultipleMyeloma/57092 Multi-Target Drug Blocks Myeloma Proliferation. March 2016]{{cite journal |author=Deepak Perumal |title=Abstract 1324: Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 is effective in vitro and in vivo in Multiple Myeloma |journal=Cancer Research |year=2014 |doi=10.1158/1538-7445.AM2014-1324|display-authors=etal |volume=74 |issue=19_Supplement |pages=1324}}

ARK5 promotes tumor cell survival under regulation by Akt.

ARK5 increases MT1-MMP production. (MT1-MMP activates MMP-2 and MMP-9 which are involved in tumor metastasis.)

As a drug target

ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.

Interactions

NUAK1 has been shown to interact with USP9X{{cite journal |last=Al-Hakim |first=Abdallah K |author2=Zagorska Anna |author3=Chapman Louise |author4=Deak Maria |author5=Peggie Mark |author6=Alessi Dario R |date=Apr 2008 |title=Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains |journal=Biochem. J. |volume=411 |issue=2 |pages=249–60 |location = England| pmid = 18254724 |doi = 10.1042/BJ20080067 |s2cid=13038944 |url=https://hal.archives-ouvertes.fr/hal-00478950/file/PEER_stage2_10.1042%252FBJ20080067.pdf }} and Ubiquitin C.