Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms

Chun, Kukjin; Cho, Seung-Ju; Choi, Joon-Seok; Kim, Sehee; Kim, Kyu‐Won; Lee, Seung-Ki

doi:10.1016/j.bbrc.2006.11.131

Cited by 19 publications

(37 citation statements)

References 18 publications

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“…We previously identified several ARD1 variants and suggested that they have distinct biological functions (6,7). We also reported that hARD1 235 undergoes autoacetylation that enhances its cell proliferative activity (11 , and hARD1…”

Section: Discussionmentioning

confidence: 96%

“…Subsequently, mammalian ARD1 was identified and is known to acetylate lysine residues of several proteins, including hypoxia-inducible factor-1α (HIF-1α), β-catenin, myosin light chain kinase, the androgen receptor, and the tubulin complex (2)(3)(4)(5). Several ARD1 variants produced from alternative splicing of mRNA have been identified in mouse and human cells (6,7). Thus far, three mouse (mARD1198, mARD1 225 , mARD1 235 ) and two human (hARD1131, hARD1 235 ) ARD1 variants were reported.…”

Section: Ard1 Was Originally Described As N-acetyltransferase Inmentioning

confidence: 99%

“…Indeed, more than half of all mammalian genes are alternatively spliced, and diverse transcripts produced from alternative splicing often have distinct functions (28,29). Alternative splicing of exon 8 of mouse ARD1 leads to the production of discrete ARD1 isoforms (mARD1 225 and mARD1 235 ) that have distinct functions in tumorigenesis (7). Different subcellular localizations of mARD1 225 and mARD1 235 may correlate with their distinct functions (7).…”

mentioning

confidence: 99%

“…Alternative splicing of exon 8 of mouse ARD1 leads to the production of discrete ARD1 isoforms (mARD1 225 and mARD1 235 ) that have distinct functions in tumorigenesis (7). Different subcellular localizations of mARD1 225 and mARD1 235 may correlate with their distinct functions (7). In contrast to mice, alternative splicing of ARD1 exon 8 does not occur in humans.…”

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confidence: 99%

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Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis

Seo

Park

Lee

et al. 2014

International Journal of Oncology

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225 autoacetylation inhibited tumor angiogenesis by decreasing the stability of hypoxia-inducible factor-1α (HIF-1α). Autoacetylation stimulated the catalytic activity of mARD1 225 to acetylate Lys532 of the oxygen-dependent degradation (ODD) domain of HIF-1α, leading to the proteosomal degradation of HIF-1α. In contrast, autoacetylation of mARD1 235 and hARD1 235 contributed to cellular growth under normoxic conditions by increasing the expression of cyclin D1. Taken together, these data suggest that autoacetylation of ARD1 variants differentially regulates angiogenesis and cell proliferation in an isoform-specific manner.

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Section: Discussionmentioning

confidence: 96%

Section: Ard1 Was Originally Described As N-acetyltransferase Inmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis

Seo

Park

Lee

et al. 2014

International Journal of Oncology

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“…Such a possibility of differential regulation of protein isoforms is not without precedence. For example, the ARD1 (Arrest defective 1 protein) gene encodes two isoforms-ARD1 235 and ARD1 225 are expressed in mouse, while ARD1 235 is expressed only in humans [73]. It was shown that both of these isoforms are regulated by different mechanisms in a species-specific manner suggesting that they have different functions in the cell.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Han

Valdez

et al. 2017

Free Radical Biology and Medicine

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A B S T R A C TThe Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability. Addition of O-GlcNAc decreases ubiquitination and degradation of Nrf1a. Transcriptional activation by Nrf1a is increased by OGT overexpression and treatment with PUGNAc. Together, these data suggest that OGT can act as a regulator of Nrf1a.

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Protein kinase C‐δ interacts with and phosphorylates ARD1

Chun

Cho

Lee

et al. 2020

Journal Cellular Physiology

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Protein kinase C-δ (PKCδ) is a diacylglycerol-dependent, calcium-independent novel PKC isoform that is engaged in various cell signaling pathways, such as cell proliferation, apoptosis, inflammation, and oxidative stress. In this study, we searched for proteins that bind PKCδ using a yeast two-hybrid assay and identified murine arrest-defective 1 (mARD1) as a binding partner. The interaction between PKCδ and mARD1 was confirmed by glutathione S-transferase pull-down and coimmunoprecipitation assays. Furthermore, recombinant PKCδ phosphorylated fulllength mARD1 protein. The NetPhos online prediction tool suggested PKCδ phosphorylates Ser 80 , Ser 108 , and Ser 114 residues of mARD1 with the highest probability. Based on these results, we synthesized peptides containing these sites and examined their phosphorylations using recombinant PKCδ. Autoradiography confirmed these sites were efficiently phosphorylated. Consequent mass spectrometry and peptide sequencing in combination with MALDI-TOF MS/MS confirmed that Ser 80 and Ser 108 were major phosphorylation sites. The alanine mutations of Ser 80 and Ser 108 abolished the phosphorylation of mARD1 by PKCδ in 293T cells supporting these observations. In addition, kinase assays using various PKC isotypes showed that Ser 80 of ARD1 was phosphorylated by PKCβI and PKCζ isotypes with the highest selectivity, while Ser 108 and/or Ser 114 were phosphorylated by PKCγ with activities comparable to that of the PKCδ isoform. Overall, these results suggest the possibility that PKCδ transduces signals by regulating phosphorylation of ARD1.

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Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms

Cited by 19 publications

References 18 publications

Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis

Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Protein kinase C‐δ interacts with and phosphorylates ARD1

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