Nuclear actin dynamics in gene expression and genome organization

Kyheröinen, Salla; Vartiainen, Maria K.

doi:10.1016/j.semcdb.2019.10.012

Cited by 33 publications

(23 citation statements)

References 100 publications

(151 reference statements)

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“…Among these protein partners, NPM was the focus of this work since, besides its large involvement in DNA repair pathways and under different stimuli, the post-translational regulation of NPM remains unexplored under the prism of genomic stability. Despite being considered a phosphoprotein with phosphorylations on threonine 199, 234, and 237 that allow functions in centriole duplication (Chan and Lim, 2015), and in the expression of DNA repair genes (Koike et al, 2010;Kyheröinen and Vartiainen, 2019;López et al, 2020), the identification of tyrosine phosphorylation on NPM and its biochemical functions have not yet been explored.…”

Section: Discussionmentioning

confidence: 99%

Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability

Russo

Ferruzo

Forti

2021

Front. Cell Dev. Biol.

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The dual-specificity phosphatase 3 (DUSP3), an atypical protein tyrosine phosphatase (PTP), regulates cell cycle checkpoints and DNA repair pathways under conditions of genotoxic stress. DUSP3 interacts with the nucleophosmin protein (NPM) in the cell nucleus after UV-radiation, implying a potential role for this interaction in mechanisms of genomic stability. Here, we show a high-affinity binding between DUSP3-NPM and NPM tyrosine phosphorylation after UV stress, which is increased in DUSP3 knockdown cells. Specific antibodies designed to the four phosphorylated NPM’s tyrosines revealed that DUSP3 dephosphorylates Y29, Y67, and Y271 after UV-radiation. DUSP3 knockdown causes early nucleolus exit of NPM and ARF proteins allowing them to disrupt the HDM2-p53 interaction in the nucleoplasm after UV-stress. The anticipated p53 release from proteasome degradation increased p53-Ser15 phosphorylation, prolonged p53 half-life, and enhanced p53 transcriptional activity. The regular dephosphorylation of NPM’s tyrosines by DUSP3 balances the p53 functioning and favors the repair of UV-promoted DNA lesions needed for the maintenance of genomic stability.

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Section: Discussionmentioning

confidence: 99%

Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability

Russo

Ferruzo

Forti

2021

Front. Cell Dev. Biol.

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“…ANLN is also known to bind transcription factors such as TAF10, Myc, and BRCA1, so ANLN is likely to be involved in chromatin organization, transcription, and DNA damage repair in the nucleus, respectively [70,92]. Recent reports found that the regulation of actin polymerization in the nucleus is required for transcription activation, cell cycle progression and DNA repair [106,107]. The role of ANLN, an actin-binding protein, has yet to be determined, but it is likely to play a role in the regulation of actin monomer or polymerization processes in the nuclei.…”

Section: Anln In Nucleusmentioning

confidence: 99%

Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target

Tuan

Lee

2020

Cancers

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Anillin (ANLN), an actin-binding protein, reportedly plays a vital role in cell proliferation and migration, particularly in cytokinesis. Although there have been findings pointing to a contribution of ANLN to the development of cancer, the association of ANLN to cancer remains not fully understood. Here, we gather evidence to determine the applicability of ANLN as a prognostic tool for some types of cancer, and the impact that ANLN has on the hallmarks of cancer. We searched academic repositories including PubMed and Google Scholar to find and review studies related to cancer and ANLN. The conclusion is that ANLN could be a potent target for cancer treatment, but the roles ANLN, other than in cytokinesis and its influence on tumour microenvironment remodeling in cancer development, must be further elucidated, and specific ANLN inhibitors should be found.

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“…β-Actin protein has also been located in the nucleus (Falahzadeh, Banaei-Esfahani, & Shahhoseini, 2015), suggesting a role in gene expression, transcription and epigenetic regulation in the nucleus (Hofmann et al, 2004;Olson & Nordheim, 2010;Visa & Percipalle, 2010;Xu, Thuraisingam, Morais, Rola-Pleszczynski, & Radzioch, 2010;Zheng, Han, Bernier, & Wen, 2009). These functions have been recently reviewed elsewhere (Kyheroinen & Vartiainen, 2019).…”

Section: Functionsmentioning

confidence: 99%

Time for rethinking the different β‐actin transgenic mouse models?

2020

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The actin family is crucial for many cellular processes and in mammals muscle and non‐muscle forms exist. The latter group contains cytoplasmic‐β‐actin and cytoplasmic‐γ‐actin, almost identical in amino acid sequence and with a significant functional overlap. We introduce the properties of the Actb gene and mRNA transcript(s) with main focus on the 3′UTR and its unique features, that is, the zipcode and two polyadenylation sites creating transcripts of different lengths. Several transgenic mouse models with a modified Actb locus have been created. The different mouse models can be divided into three groups; that is, 5′ or 3′ insertion models, mouse models with loxP sequences around exon 2–3 resulting in deletion the start codon, and models with gene edited Actb sequences that produces γ‐actin protein instead of β‐actin. Whole body knockouts and, with one exception, insertion models lead to embryonic lethality indicating that the Actb gene or transcripts or translated β‐actin are essential. Tissue specific ablation at later developmental stages lead to no, or mild phenotypes, suggesting that the Actb gene or β‐actin protein is somewhat dispensable. Gene edited Actb mice that produce γ‐actin are viable. This assumes that the nucleotide sequence of Actb is important and not the specific amino acid sequence of the protein it encodes. Upregulation of other actin paralogs was frequently observed upon β‐actin ablation and can also engage in the phenotype. For a better understanding, it will be necessary to analyze in current and future models all relevant actin transcripts and protein levels in a standardized and comprehensive way.

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Nuclear actin dynamics in gene expression and genome organization

Cited by 33 publications

References 100 publications

Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability

Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability

Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target

Time for rethinking the different β‐actin transgenic mouse models?

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