NUAK1

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NUAK1
Identifiers
Aliases NUAK1, ARK5, NUAK family kinase 1
External IDs MGI: 1925226 HomoloGene: 8896 GeneCards: NUAK1
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_014840

NM_001004363

RefSeq (protein)

NP_055655
NP_055655.1

NP_001004363.1
NP_001004363

Location (UCSC) Chr 12: 106.06 – 106.14 Mb Chr 10: 84.37 – 84.44 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/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.[3][4][5]


Function[edit]

Clinical significance[edit]

ARK5 is important in tumor malignancy and invasiveness.[6]

Research findings[edit]

ARK5 is often overexpressed in multiple myeloma cell lines.[7][8] ARK5 promotes tumor cell survival under regulation by Akt.[6]

ARK5 increases MT1-MMP production.[6] (MT1-MMP activates MMP-2 and MMP-9 which are involved in tumor metastasis.[6])

As a drug target[edit]

ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.[7]

Interactions[edit]

NUAK1 has been shown to interact with USP9X[9] and Ubiquitin C.[9]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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". J Biol Chem. 278 (1): 48–53. doi:10.1074/jbc.M206025200. PMID 12409306. 
  4. ^ 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. 
  5. ^ "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1". 
  6. ^ 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 381626Freely accessible. PMID 15060171. 
  7. ^ a b Multi-Target Drug Blocks Myeloma Proliferation. March 2016
  8. ^ 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. 
  9. ^ 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". Biochem. J. England. 411 (2): 249–60. doi:10.1042/BJ20080067. PMID 18254724. 

Further reading[edit]