2011
DOI: 10.1038/onc.2011.19
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A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation

Abstract: It has been suggested that adenosine monophosphateactivated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylat… Show more

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Cited by 68 publications
(61 citation statements)
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“…Nonpeptide inhibitors have only recently been described for CASP6 (32,33), but these inhibitors also target the active site of the enzyme. ARK5 inhibits both activation and activity of CASP6 by phosphorylation, and it regulates the expression level of CASP6 indirectly because it phosphorylates and suppresses p53 (34), and CASP6 is directly transactivated by p53 (35). These functions make AKR5 a potential therapeutic target.…”
Section: Discussionmentioning
confidence: 99%
“…Nonpeptide inhibitors have only recently been described for CASP6 (32,33), but these inhibitors also target the active site of the enzyme. ARK5 inhibits both activation and activity of CASP6 by phosphorylation, and it regulates the expression level of CASP6 indirectly because it phosphorylates and suppresses p53 (34), and CASP6 is directly transactivated by p53 (35). These functions make AKR5 a potential therapeutic target.…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, nuclear localization has also been reported for the zinc-finger-containing M-line protein UNC-98/ZnF (Mercer et al 2003). The mammalian UNC-82 orthologs exhibit nuclear localization under conditions of stress (Kuga et al 2008;Hou et al 2011). The colocalization of paramyosin and the mutant UNC-82 E424K protein in the distinctive accumulations suggests that the two proteins interact physically during assembly of the thick filament, and that loss of UNC-82 catalytic activity leads to aggregation of both proteins.…”
Section: Mutant Unc-82 E424k Colocalizes With Abnormal Paramyosin Accmentioning
confidence: 82%
“…NUAK1 was first described as supporting AKT-dependent cell survival during nutrient starvation (Suzuki et al, 2003), and has been shown to induce p53 phosphorylation (Hou et al, 2011). NUAK1 expression is now known to be closely associated with metastases, colorectal cancer and is an indicator of poor prognoInt.…”
Section: Abstract: Nuak Chick Embryo In Situ Hybridizationmentioning
confidence: 99%
“…Unlike AMPK, which is activated under various stress conditions resulting in decreased ATP concentrations (Scott et al, 2007), ARKs do not have AMP: ATP ratio-sensitive regulatory subunits. Thus, they do not directly participate in adaptive responses to energy balance (Al-Hakim et al, 2005).NUAK1 was first described as supporting AKT-dependent cell survival during nutrient starvation (Suzuki et al, 2003), and has been shown to induce p53 phosphorylation (Hou et al, 2011). NUAK1 expression is now known to be closely associated with metastases, colorectal cancer and is an indicator of poor prognoInt.…”
mentioning
confidence: 99%