NUAK1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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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.[1][2][3]


Function

Clinical significance

ARK5 is important in tumor malignancy and invasiveness.[4]

Research findings

ARK5 is often overexpressed in multiple myeloma cell lines.[5][6] ARK5 promotes tumor cell survival under regulation by Akt.[4]

ARK5 increases MT1-MMP production.[4] (MT1-MMP activates MMP-2 and MMP-9 which are involved in tumor metastasis.[4])

As a drug target

ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.[5]

Interactions

NUAK1 has been shown to interact with USP9X[7] and Ubiquitin C.[7]

References

  1. 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.
  2. 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.
  3. "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1".
  4. 4.0 4.1 4.2 4.3 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.
  5. 5.0 5.1 Multi-Target Drug Blocks Myeloma Proliferation. March 2016
  6. 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.
  7. 7.0 7.1 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



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