NUAK1

Full Name

NUAK Family Kinase 1

Function

Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. 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. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316).

Biological Process

Cell adhesionIEA:UniProtKB-KW
Cellular response to DNA damage stimulusIEA:UniProtKB-KW
Cellular response to glucose starvationManual Assertion Based On ExperimentIBA:GO_Central
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cell adhesionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cell population proliferationManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of cellular senescenceManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of myosin-light-chain-phosphatase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of signal transduction by p53 class mediatorTAS:Reactome

Cellular Location

Nucleus
Cytoplasm

PTM

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X.
Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation with IGF1.