p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

Morelli, Gabriele; Even, Aviel; Gladwyn-Ng, Ivan; Bail, Romain Le; Shilian, Michal; Godin, Juliette D.; Peyre, Elise; Hassan, Bassem A.; Besson, Arnaud; Rigo, Jean-Michel; Weil, Miguel; Brône, Bert; Nguyen, Laurent

doi:10.1016/j.celrep.2018.04.083

Cited by 32 publications

(58 citation statements)

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“…Our recent data in mouse and human cancer cells support this hypothesis and suggest that p27 C-terminus, impacting on MT-dynamics via stathmin, can also regulate vesicle recycling, Ras signaling and, eventually, cell cycle entry and proliferation [17, 19, 33]. Similarly, the new work of Nguyen et al support the evidence that p27-mediated MT-acetylation, via α-TAT1 regulation, is necessary for vesicle transport along axons, in neurons [12]. Moreover, it is possible that the lack of p27 C-terminus could lead to a decreased protein stability, as recently shown, for instance, in the case of T197A knock-in mice that display most of the phenotypes described in p27 null animals [36].…”

Section: Main Textmentioning

confidence: 84%

“…Nguyen et al have recently observed that, in murine cortical neurons, p27 is located in multiple cytoplasmic compartments, including both dendrites and axons [12]. Projections from p27 knock out (p27 KO ) neurons displayed a reduced instantaneous and average transport velocity compared to wild-type (p27 WT ) controls.…”

Section: Main Textmentioning

confidence: 99%

“…Although this phenotype seems to be linked to a cytoplasmic localization of p27, it has not been clearly linked to alterations of the cytoskeleton dynamics. However, this phenotype is highly reminiscent of the motor behaviour of larvs knocked down for Dacapo (the drosophila ortholog of p27) that showed reduced crawling speed and peristaltic waves followed by climbing defects in adult life [12].…”

Section: Main Textmentioning

confidence: 99%

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p27kip1 at the crossroad between actin and microtubule dynamics

et al. 2019

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The p27 kip1 protein, mainly known as a negative regulator of cell proliferation, has also been involved in the control of other cellular processes, including the regulation of cytoskeleton dynamics. Notably, these two functions involve distinct protein domains, residing in the N- and C-terminal halves, respectively. In the last two decades, p27 kip1 has been reported to interact with microtubule and acto-myosin cytoskeletons, both in direct and indirect ways, overall drawing a picture in which several factors play their role either in synergy or in contrast one with another. As a result, the role of p27 kip1 in cytoskeleton dynamics has been implicated in cell migration, both in physiologic and in neoplastic contexts, modulating cytokinesis, lipid raft trafficking, and neuronal development. Recently, two distinct papers have further reported a central role for p27 kip1 in the control of microtubule stability and post-translational modifications, dissecting the interaction between p27 kip1 and α-tubulin-acetyl-transferase (α-TAT), an enzyme involved in the stability of microtubules, and protein-regulator of cytokinesis 1 (PRC1), a nuclear regulator of the central spindle during mitosis. In light of these recent evidences, we will comment on the role of p27 kip1 on cytoskeleton regulation and its implication for cancer progression.

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Section: Main Textmentioning

confidence: 84%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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p27kip1 at the crossroad between actin and microtubule dynamics

et al. 2019

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“…Recently, the Nguyen group also discovered, in mice cortical neurons, the involvement of p27 in the stabilization of alpha-tubulin acetyl transferase 1 (alpha-TAT1), the principal enzyme involved in MT post-translational modifications [ 73 ], adding important pieces of information to the comprehension of p27′s activity on MT cytoskeleton dynamics in vesicle trafficking and neuron migration. In addition, the cytoplasmic CDKI is involved in the enhancement of epithelial–mesenchymal transition, a well-known pro-carcinogenic process, by inducing Twist1 upregulation via the activation of STAT3 [ 74 ].…”

Section: P27 and P57 Proteins’ Major Features Properties And Funmentioning

confidence: 99%

Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols

et al. 2020

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In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, the cell division cycle and its control strongly influence cell destiny, playing a critical role in targeting it towards a specific phenotype. Several factors participate in the control of growth, and among them, p27Kip1 and p57Kip2, two proteins modulating various transitions of the cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing, in particular, on their recently identified roles not directly correlated with cell cycle modulation. Then, their possible roles as molecular effectors of polyphenols’ activities will be discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to exhibit promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for improving their clinical effects and for diminishing their negative side activities. The importance of p27Kip1 and p57Kip2 in polyphenols’ cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.

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“…Recently, Nguyen group also discovered in mice cortical neurons the involvement of p27 in the stabilization of alpha-tubulin acetyl transferase 1 (alpha-TAT1), the principal enzyme involved in MT post-translational modifications [73], adding important pieces of information to the comprehension of p27 activity on MT cytoskeleton dynamics in vesicles trafficking and neuron migration. In addition, the cytoplasmic CDKI is involved in the enhancement of epithelial-mesenchymal transition, a well-known pro-carcinogenetic process, by inducing Twist1 up-regulation via activation of STAT3 [74].…”

Section: P27: a Key Ambiguous Protein With Multiple Contrasting Rolesmentioning

confidence: 99%

Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols

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Cervellera

et al. 2020

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In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, cell division cycle and its control strongly influence cell destiny playing a critical role in targeting it towards a specific phenotype. Several factors participate to the control of growth and among them p27 and p57, two proteins modulating various transitions of cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing in particular on their recently identified roles not directly correlated to cell cycle modulation. Then, their possible role as molecular effectors of polyphenols activities are discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to play promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for ameliorating their clinical effects and for diminishing their negative side activities. The importance of p27 and p57 in polyphenol cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.

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p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

Cited by 32 publications

References 38 publications

p27kip1 at the crossroad between actin and microtubule dynamics

p27kip1 at the crossroad between actin and microtubule dynamics

Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols

Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols

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