Versatility of ARD1/NAA10-mediated protein lysine acetylation

Vo, Tam Thuy Lu; Jeong, Chul‐Ho; Lee, Sooyeun; Kim, Kyu‐Won; Ha, Eunyoung; Seo, Ji Hae

doi:10.1038/s12276-018-0100-7

Cited by 12 publications

(7 citation statements)

References 108 publications

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“…Analysis for its gene expression or protein amount might not reflect the specific characteristics of NAA10 as an acetyltransferase enzyme. Many previous studies support that NAT and KAT activities of NAA10 are essential for its biological roles and that NAA10 function is stimulated by protein modifications rather than gene expression [65]. Therefore, the development of new methods detecting enzyme activity or different modified forms of NAA10 in cancer tissues could be helpful to provide more accurate information.…”

Section: Discussionmentioning

confidence: 94%

NAA10 as a New Prognostic Marker for Cancer Progression

Kim

et al. 2020

IJMS

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N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.

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Section: Discussionmentioning

confidence: 94%

NAA10 as a New Prognostic Marker for Cancer Progression

Kim

et al. 2020

IJMS

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“…Also known as N-α-acetyltransferase 10 (NAA10), is an N-acetyltransferase (NAT) enzyme that belongs to the GCN5-related N-acetyltransfererase (GNAT) superfamily that is widely-known to catalyze the transfer of an acetyl group from acetyl coenzyme A to the target protein’s N-terminal amino acid ( 107 ). Although ARD1 is best known for its role as a NAT, accumulating evidence has revealed that ARD1 also exhibits KAT activity and can acetylate many proteins including HIF-1α, β-catenin, myosin light chain kinase (MLCK), runt-related transcription factor 2 (Runx2), phosphoglycerate kinase 1 (PGK1), heat shock protein 70 (Hsp70), and androgen receptor ( 107 , 108 ). Important roles for ARD1 have been detected in a wide variety of cellular activities like cell division, proliferation, hypoxia, apoptosis, and autophagy ( 107 ).…”

Section: Ard1 (Arrest-defective 1 Protein)mentioning

confidence: 99%

“…Although ARD1 is best known for its role as a NAT, accumulating evidence has revealed that ARD1 also exhibits KAT activity and can acetylate many proteins including HIF-1α, β-catenin, myosin light chain kinase (MLCK), runt-related transcription factor 2 (Runx2), phosphoglycerate kinase 1 (PGK1), heat shock protein 70 (Hsp70), and androgen receptor ( 107 , 108 ). Important roles for ARD1 have been detected in a wide variety of cellular activities like cell division, proliferation, hypoxia, apoptosis, and autophagy ( 107 ). Not surprisingly, researchers have found the aberrant expression and deregulated KAT activity of ARD1 contributes to different cancers including lung, liver, breast, cervical, bladder, and colorectal cancers ( 107 , 109 , 110 ).…”

Section: Ard1 (Arrest-defective 1 Protein)mentioning

confidence: 99%

“…Important roles for ARD1 have been detected in a wide variety of cellular activities like cell division, proliferation, hypoxia, apoptosis, and autophagy ( 107 ). Not surprisingly, researchers have found the aberrant expression and deregulated KAT activity of ARD1 contributes to different cancers including lung, liver, breast, cervical, bladder, and colorectal cancers ( 107 , 109 , 110 ). The human ARD1 protein consists of 235 amino acid residues with a well-conserved N-acetyltransferase domain that contains an acetyl-CoA-binding site, a putative nuclear localization signal (NLS), and a highly variable C-terminal region, recognized in different ARD1 variants derived from alternative RNA splicing ( Figure 2A ) ( 111 , 112 ).…”

Section: Ard1 (Arrest-defective 1 Protein)mentioning

confidence: 99%

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Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer

Jaiswal

Agarwal²,

Gupta³

2022

Front. Endocrinol.

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The development and growth of a normal prostate gland, as well as its physiological functions, are regulated by the actions of androgens through androgen receptor (AR) signaling which drives multiple cellular processes including transcription, cellular proliferation, and apoptosis in prostate cells. Post-translational regulation of AR plays a vital role in directing its cellular activities via modulating its stability, nuclear localization, and transcriptional activity. Among various post-translational modifications (PTMs), acetylation is an essential PTM recognized in AR and is governed by the regulated actions of acetyltransferases and deacetyltransferases. Acetylation of AR has been identified as a critical step for its activation and depending on the site of acetylation, the intracellular dynamics and activity of the AR can be modulated. Various acetyltransferases such as CBP, p300, PCAF, TIP60, and ARD1 that are known to acetylate AR, may directly coactivate the AR transcriptional function or help to recruit additional coactivators to functionally regulate the transcriptional activity of the AR. Aberrant expression of acetyltransferases and their deregulated activities have been found to interfere with AR signaling and play a key role in development and progression of prostatic diseases, including prostate cancer (PCa). In this review, we summarized recent research advances aimed at understanding the role of various lysine acetyltransferases (KATs) in the regulation of AR activity at the level of post-translational modifications in normal prostate physiology, as well as in development and progression of PCa. Considering the critical importance of KATs in modulating AR activity in physiological and patho-physiological context, we further discussed the potential of targeting these enzymes as a therapeutic option to treat AR-related pathology in combination with hormonal therapy.

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“…Crystallographic structure analysis also showed that hARD1/NAA10 lacks enough space to perform lysine acetylation of substrate proteins, implicative of its role only as NAT rather than KAT [17,18]. Based on these controversial results on the KAT activity of hARD1/NAA10, some studies suggest that the KAT activity of hARD1 could be activated under some specific conditions or was very weak in vitro [19,20]. Therefore, further studies are warranted to reconcile these opposing views on the KAT activity of hARD1/NAA10.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Lysine Acetyltransferase Activity of Recombinant Human ARD1/NAA10

Park

Lee

et al. 2020

Molecules

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Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its’ role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration.

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Versatility of ARD1/NAA10-mediated protein lysine acetylation

Cited by 12 publications

References 108 publications

NAA10 as a New Prognostic Marker for Cancer Progression

NAA10 as a New Prognostic Marker for Cancer Progression

Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer

Characterization of Lysine Acetyltransferase Activity of Recombinant Human ARD1/NAA10

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