α-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell–substrate adhesion

Aguilar, Andrea; Becker, Lars; Tedeschi, Thomas; Heller, Stefan; Iomini, Carlo; Nachury, Maxence V.

doi:10.1091/mbc.e13-10-0609

Cited by 79 publications

(88 citation statements)

References 69 publications

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“…This is one possible mechanism to ensure microtubule acetylation at the leading edge for promoting directional cell migration [129]. It was also reported that tubulin acetylation is required for cellcell contact inhibition and cell adhesion [51]. Decreased dynamics of acetylated microtubules induced by HDAC6 inhibition affects turnover of cellular focal adhesion [130].…”

Section: Tubulin Acetylation and Intracellular Transportmentioning

confidence: 98%

“…They possess intrinsic a-tubulin acetyltransferase activity [47,48]. Moreover, ATAT1 functions as a bona-fide tubulin acetyltransferase in vivo, because deletion of the mouse gene leads to nearly complete loss of tubulin acetylation in embryos and various tissues [49][50][51]. Thus, ATAT1 is now considered as a major tubulin acetyltransferase in mammals.…”

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

“…By staining for bgalactosidase activity in Atat1 LacZ mice, it was shown that Atat1 is expressed in a variety of tissues, with the strongest expression in the central nervous system and various other ciliated tissues, including the testis, lung, eye and inner ear (Li and Yang, unpublished data) [49]. In knockout mice, Atat1 deficiency leads to nearly total loss of tubulin acetylation but does not affect animal survival [49][50][51]. Except for some brain and sperm abnormalities, mutant mice develop rather normally [49][50][51].…”

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

“…In knockout mice, Atat1 deficiency leads to nearly total loss of tubulin acetylation but does not affect animal survival [49][50][51]. Except for some brain and sperm abnormalities, mutant mice develop rather normally [49][50][51]. The brain abnormalities include alteration of the dentate gyrus and dilation in the lateral ventricles (Li and Yang, unpublished data) [49].…”

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

“…Knockdown of Atat1 or Elp3 expression revealed that tubulin acetylation is important for neuronal migration [40,126]. However, ELP3 is unlikely a major tubulin acetyltransferase in vivo [49][50][51], so impaired neuronal migration observed in Elp3-deficient mice may be due to other mechanisms [40]. Of relevance, ELP3 proteins from different organisms are able to modify the anticodon of tRNA [127].…”

Section: Tubulin Acetylation and Intracellular Transportmentioning

confidence: 99%

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Tubulin acetylation: responsible enzymes, biological functions and human diseases

Yang

2015

Cell. Mol. Life Sci.

213

184

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Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function.

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Section: Tubulin Acetylation and Intracellular Transportmentioning

confidence: 98%

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

Section: Tubulin Acetyltransferases and Deacetylases Identification Amentioning

confidence: 99%

Section: Tubulin Acetylation and Intracellular Transportmentioning

confidence: 99%

See 3 more Smart Citations

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Yang

2015

Cell. Mol. Life Sci.

213

184

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Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models

Depetter

Geurs

Vreese

et al. 2019

Intl Journal of Cancer

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Our study investigates the biochemical and functional impact of selective histone deacetylase 6 (HDAC6) inhibitors, a promising class of novel therapeutics, in several cancer models. Selective HDAC6 inhibitors (Tubathian A, Tubastatin A, Tubacin and Ricolinostat) and a non‐selective HDAC inhibitor (Vorinostat) were evaluated on cancer cell lines derived from multiple tumour types in both an in vitro and in vivo setting as potential cancer therapeutics. Selective HDAC6 inhibitors resulted in α‐tubulin acetylation with no impact on histone acetylation but failed to show any anti‐cancer properties. Only the use of high concentrations of selective HDAC6 inhibitors resulted in co‐inhibition of other HDAC enzymes and consequently in reduced growth, migratory and/or invasive activity of cancer cells in vitro as well as in vivo. The specificity of HDAC6 inhibition was confirmed using a CRISPR/Cas9 knockout cell line. Our results suggest that selective HDAC6 inhibitors may fall short as potential single agent anti‐cancer drugs and prove that many previous data regarding this promising class of compounds need to be interpreted with great care due to their use in high concentrations resulting in low selectivity and potential off‐target effects.

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Downregulation of SPIN90 promotes fibroblast activation via periostin‐FAK‐ROCK signaling module

You

Huh

Lee

et al. 2018

Journal Cellular Physiology

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Alterations in mechanical properties in the extracellular matrix are modulated by myofibroblasts and are required for progressive fibrotic diseases. Recently, we reported that fibroblasts depleted of SPIN90 showed enhanced differentiation into myofibroblasts via increased acetylation of microtubules in the soft matrix; the mechanisms of the underlying signaling network, however, remain unclear. In this study, we determine the effect of depletion of SPIN90 on FAK/ROCK signaling modules. Transcriptome analysis of Spin90 KO mouse embryonic fibroblasts (MEF) and fibroblasts activated by TGF‐β revealed that Postn is the most significantly upregulated gene. Knockdown of Postn by small interfering RNA suppressed cell adhesion and myofibroblastic differentiation and downregulated FAK activity in Spin90 KO MEF. Our results indicate that SPIN90 depletion activates FAK/ROCK signaling, induced by Postn expression, which is critical for myofibroblastic differentiation on soft matrices mimicking the mechanical environment of a normal tissue.

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α-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell–substrate adhesion

Cited by 79 publications

References 69 publications

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models

Downregulation of SPIN90 promotes fibroblast activation via periostin‐FAK‐ROCK signaling module

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