NUAK1
Identifiers
AliasesNUAK1, ARK5, NUAK family kinase 1
External IDsOMIM: 608130 MGI: 1925226 HomoloGene: 8896 GeneCards: NUAK1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_014840

NM_001004363

RefSeq (protein)

NP_055655
NP_055655.1

NP_001004363

Location (UCSC)Chr 12: 106.06 – 106.14 MbChr 10: 84.21 – 84.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7]

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.[8]

Clinical significance

ARK5 is important in tumor malignancy and invasiveness.[9]

Research findings

ARK5 is often overexpressed in multiple myeloma cell lines.[10][11] ARK5 promotes tumor cell survival under regulation by Akt.[9]

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

As a drug target

ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.[10]

Interactions

NUAK1 has been shown to interact with USP9X[12] and Ubiquitin C.[12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000074590 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020032 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H (Dec 2002). "Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein" (PDF). J Biol Chem. 278 (1): 48–53. doi:10.1074/jbc.M206025200. PMID 12409306. S2CID 23605132.
  6. ^ Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Esumi H (Sep 2003). "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". Oncogene. 22 (40): 6177–82. doi:10.1038/sj.onc.1206899. PMID 13679856.
  7. ^ "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1".
  8. ^ Protein Coding (2021-11-14). "NUAK1 Gene - NUAK Family Kinase 1". Gene Cards. Retrieved 2021-12-19.
  9. ^ a b c d Suzuki A, Lu J, Kusakai G et al. (2004). "ARK5 is a tumor invasion-associated factor downstream of Akt signaling". Mol. Cell. Biol. 24 (8): 3526–35. doi:10.1128/MCB.24.8.3526-3535.2004. PMC 381626. PMID 15060171.((cite journal)): CS1 maint: uses authors parameter (link)
  10. ^ a b Multi-Target Drug Blocks Myeloma Proliferation. March 2016
  11. ^ Deepak Perumal et al. (2014). "Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 is effective in vitro and in vivo in Multiple Myeloma". Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res. 74: 1324. doi:10.1158/1538-7445.AM2014-1324.((cite journal)): CS1 maint: uses authors parameter (link)
  12. ^ a b Al-Hakim, Abdallah K; Zagorska Anna; Chapman Louise; Deak Maria; Peggie Mark; Alessi Dario R (Apr 2008). "Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains" (PDF). Biochem. J. England. 411 (2): 249–60. doi:10.1042/BJ20080067. PMID 18254724.

Further reading