p27kip1 at the crossroad between actin and microtubule dynamics
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(2019) 14:2 Rampioni Vinciguerra et al. Cell Div https://doi.org/10.1186/s13008-019-0045-9
Open Access
COMMENTARY
p27kip1 at the crossroad between actin and microtubule dynamics Gian Luca Rampioni Vinciguerra1,2, Francesca Citron1, Ilenia Segatto1, Barbara Belletti1, Andrea Vecchione2 and Gustavo Baldassarre1*
Abstract The p27kip1 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, p 27kip1 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 p27kip1 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 p27kip1 in the control of microtubule stability and post-translational modifications, dissecting the interaction between p27kip1 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 p 27kip1 on cytoskeleton regulation and its implication for cancer progression. Keywords: p27, Microtubule, Actin, Cytoskeleton, Stathmin, Migration, Cancer Background p27kip1 (hereafter p27) is a member of the CIP/KIP family of cyclin-dependent kinase (CDK) inhibitors (CKI), also comprising p21waf1 and p57kip2. These CKIs are negative regulators of cell proliferation, mainly working by impairing the activity of cyclin-CDK complexes in the cell nucleus [1]. However, their involvement in CDK-independent functions, such as cell migration and, more in general, cytoskeletal remodeling have also emerged [1]. Indeed, all three members of the CIP/KIP CKI family have been shown to interfere with the pathway of RhoA, a GTPase that regulates actin remodeling and cell migration when located in the cytoplasm [1]. In particular, it has been reported that cytoplasmic p 21waf1 can directly bind Rho-kinase (ROCK), inhibiting stress fiber formation *Correspondence: [email protected] 1 Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy Full list of author information is available at the end of the article
and regulating neurite outgrowth in Ras-transformed NIH3T3 cells [2, 3], and that p 57kip2 can reduce motility in HeLa cells, regulating the actin cytoskeleton via LIMkinase1, a well-known downstream effector of ROCK [4]. The capability to shuttle from the nucleus to
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