Biology:NUAK1
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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
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.[4]
Clinical significance
ARK5 is important in tumor malignancy and invasiveness.[5]
Research findings
ARK5 is often overexpressed in multiple myeloma cell lines.[6][7] ARK5 promotes tumor cell survival under regulation by Akt.[5]
ARK5 increases MT1-MMP production.[5] (MT1-MMP activates MMP-2 and MMP-9 which are involved in tumor metastasis.[5])
As a drug target
ON123300 (a CDK4 inhibitor), also inhibits ARK5 and reduces proliferation of multiple myeloma and mantle cell lymphoma cell lines.[6]
Interactions
NUAK1 has been shown to interact with USP9X[8] and Ubiquitin C.[8]
References
- ↑ "Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein". J Biol Chem 278 (1): 48–53. Dec 2002. doi:10.1074/jbc.M206025200. PMID 12409306. http://espace.library.uq.edu.au/view/UQ:65358/UQ65358_OA.pdf.
- ↑ "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. Sep 2003. doi:10.1038/sj.onc.1206899. PMID 13679856.
- ↑ "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9891.
- ↑ Protein Coding (2021-11-14). "NUAK1 Gene - NUAK Family Kinase 1" (in en). https://www.genecards.org/cgi-bin/carddisp.pl?gene=NUAK1.
- ↑ 5.0 5.1 5.2 5.3 "ARK5 is a tumor invasion-associated factor downstream of Akt signaling.". Mol. Cell. Biol. 24 (8): 3526–35. 2004. doi:10.1128/MCB.24.8.3526-3535.2004. PMID 15060171.
- ↑ 6.0 6.1 Multi-Target Drug Blocks Myeloma Proliferation. March 2016
- ↑ Deepak Perumal (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.
- ↑ 8.0 8.1 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. https://hal.archives-ouvertes.fr/hal-00478950/file/PEER_stage2_10.1042%252FBJ20080067.pdf.
Further reading
- "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.". DNA Res. 5 (1): 31–9. 1998. doi:10.1093/dnares/5.1.31. PMID 9628581.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.". EMBO J. 23 (4): 833–43. 2005. doi:10.1038/sj.emboj.7600110. PMID 14976552.
- "Regulation of caspase-6 and FLIP by the AMPK family member ARK5.". Oncogene 23 (42): 7067–75. 2004. doi:10.1038/sj.onc.1207963. PMID 15273717.
- "Strong association of ARK5 with tumor invasion and metastasis.". J. Exp. Clin. Cancer Res. 23 (2): 263–8. 2005. PMID 15354411.
- "ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma.". Oncogene 24 (46): 6936–44. 2006. doi:10.1038/sj.onc.1208844. PMID 16044163.
- "14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK.". J. Cell Sci. 118 (Pt 23): 5661–73. 2006. doi:10.1242/jcs.02670. PMID 16306228.
- "NDR2 acts as the upstream kinase of ARK5 during insulin-like growth factor-1 signaling.". J. Biol. Chem. 281 (20): 13915–21. 2006. doi:10.1074/jbc.M511354200. PMID 16488889.
- "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
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