NUAK1

Last updated

NUAK1
Identifiers
Aliases NUAK1 , ARK5, NUAK family kinase 1
External IDs OMIM: 608130; MGI: 1925226; HomoloGene: 8896; GeneCards: NUAK1; OMA:NUAK1 - orthologs
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 Mb Chr 10: 84.21 – 84.28 Mb
PubMed search [3] [4]
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. [5] [6] [7]

Contents

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]

Related Research Articles

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The proto-oncogene c-Rel is a protein that in humans is encoded by the REL gene. The c-Rel protein is a member of the NF-κB family of transcription factors and contains a Rel homology domain (RHD) at its N-terminus and two C-terminal transactivation domains. c-Rel is a myeloid checkpoint protein that can be targeted for treating cancer. c-Rel has an important role in B-cell survival and proliferation. The REL gene is amplified or mutated in several human B-cell lymphomas, including diffuse large B-cell lymphoma and Hodgkin's lymphoma.

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<span class="mw-page-title-main">CBLB (gene)</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PTK6</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">BMX (gene)</span> Type of enzyme

Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene.

<span class="mw-page-title-main">MADD (gene)</span> Protein-coding gene in the species Homo sapiens

MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene. MADD is one out of four of the splice variants of the human IG20 (insulinoma-glucagonoma clone 20) gene which is located on human chromosome 11.

<span class="mw-page-title-main">RRAS2</span> Protein-coding gene in the species Homo sapiens

Ras-related protein R-Ras2 is a protein that in humans is encoded by the RRAS2 gene.

<span class="mw-page-title-main">TRIB3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">WASF3</span>

Wiskott–Aldrich syndrome protein family member 3 is a protein that in humans is encoded by the WASF3 gene.

<span class="mw-page-title-main">Cyclin-dependent kinase 3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SPRED2</span> Protein-coding gene in the species Homo sapiens

Sprouty-related, EVH1 domain-containing protein 2 is a protein that in humans is encoded by the SPRED2 gene.

<span class="mw-page-title-main">RPS6KA4</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-4 is an enzyme that in humans is encoded by the RPS6KA4 gene.

<span class="mw-page-title-main">PLK2</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase PLK2 is an enzyme that in humans is encoded by the PLK2 gene.

<span class="mw-page-title-main">LATS2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">VAV3</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.

<span class="mw-page-title-main">MELK</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MAGI3</span> Protein-coding gene in the species Homo sapiens

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 is an enzyme that in humans is encoded by the MAGI3 gene.

<span class="mw-page-title-main">STK38L</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase 38-like is an enzyme that in humans is encoded by the STK38L gene.

<span class="mw-page-title-main">LLGL1</span> Protein-coding gene in the species Homo sapiens

Lethal(2) giant larvae protein homolog 1 is a protein that in humans is encoded by the LLGL1 gene.

<span class="mw-page-title-main">TCL1B</span> Protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000074590 Ensembl, May 2017
  2. 1 2 3 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. S2CID   20975883.
  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. 1 2 3 4 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.
  10. 1 2 Multi-Target Drug Blocks Myeloma Proliferation. March 2016
  11. Deepak Perumal, et al. (2014). "Abstract 1324: Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 is effective in vitro and in vivo in Multiple Myeloma". Cancer Research. 74 (19_Supplement): 1324. doi:10.1158/1538-7445.AM2014-1324.
  12. 1 2 Al-Hakim AK, 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. 411 (2). England: 249–60. doi:10.1042/BJ20080067. PMID   18254724. S2CID   13038944.

Further reading