Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain

Obungu, Victor H.; Burns, A. Lee; Agarwal, Sunita K.; Chandrasekharapa, Settara C; Adelstein, Robert S.; Marx, Stephen J.

doi:10.1038/sj.onc.1206658

Cited by 40 publications

(22 citation statements)

References 53 publications

(68 reference statements)

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“…The key cytokinesisassociated myosin, myosin II, can be altered in neoplasia (34). As well as binding anillin (5), myosin II interacts with the metastasis-associated protein S100A4 (35) and the nuclear tumor suppressor menin (36). Clearly, then, the molecular machinery associated with cytokinesis can be deranged in neoplasia, often with altered expression.…”

Section: Discussionmentioning

confidence: 99%

The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors

Hall

Todd

Hyland

et al. 2005

Clinical Cancer Research

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Anillin is an actin-binding protein that can bind septins and is a component of the cytokinetic ring.We assessed the anillin expression in 7,579 human tissue samples and cell lines by DNA microarray analysis. Anillin is expressed ubiquitously but with variable levels of expression, being highest in the central nervous system. The median level of anillin mRNA expression was higher in tumors than normal tissues (median fold increase 2.58; 95% confidence intervals, 2.19-5.68, P < 0.0001) except in the central nervous system where anillin mRNA levels were lower in tumors.We developed a sensitive reverse transcription-PCR strategy to show that anillin mRNA is expressed in cell lines and in cDNA panels derived from fetal and adult tissues, thus validating the microarray data. We compared anillin with Ki67 mRNA expression and found a significant linear relationship between anillin and Ki67 mRNA expression (Spearmann r f 0.6, P < 0.0001). Anillin mRNA expression was analyzed during tumor progression in breast, ovarian, kidney, colorectal, hepatic, lung, endometrial, and pancreatic tumors and in all tissues there was progressive increase in anillin mRNA expression from normal to benign to malignant to metastatic disease. Finally, we used anti-anillin sera and found nuclear anillin immunoreactivity to be widespread in normal tissues, often not correlating with proliferative compartments. These data provide insight into the existence of nonproliferation-associated activities of anillin and roles in interphase nuclei. Thus, anillin is overexpressed in diverse common human tumors, but not simply as a consequence of being a proliferation marker. Anillin may have potential as a novel biomarker.

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Section: Discussionmentioning

confidence: 99%

The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors

Hall

Todd

Hyland

et al. 2005

Clinical Cancer Research

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“…Likewise, the interactions between MIIA and other proteins are just beginning to be unravelled. It has been described that this molecular motor associates with Mts1, a protein with a role in metastasis (Ford et al, 1997), and menin, a tumor suppressor (Obungu et al, 2003). In addition, nonmuscle myosin II also interacts with anillin, a protein involved in cytokinesis (Straight et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1α

Rey

Valenzuela-Fernández

Urzainqui

et al. 2007

Journal of Cell Science

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Endocytosis of chemokine receptors regulates signal transduction initiated by chemokines, but the molecular mechanisms underlying this process are not fully defined. In this work, we assessed the involvement of the motor protein nonmuscle myosin heavy chain IIA (MIIA) in the endocytosis of CXCR4 induced by SDF-1α (also known as CXCL12) in T lymphocytes. Overexpression of the C-terminal half of MIIA inhibited the ligand-induced endocytosis of CXCR4, but not that of transferrin receptor. Targeting MIIA either by silencing its expression with small interfering RNA (siRNA) or by blebbistatin treatment also inhibited endocytosis of CXCR4. Inhibition of endocytosis of CXCR4 by targeting endogenous MIIA resulted in an increased migration of T cells induced by SDF-1α, and in the inhibition of the HIV-1-Env antifusogenic activity of this chemokine. Coimmunoprecipitation and protein-protein binding studies demonstrated that MIIA interacts with both the cytoplasmic tail of CXCR4 and β-arrestin. Moreover, SDF-1α promotes a rapid MIIA-β-arrestin dissociation. Our data reveal a novel role for MIIA in CXCR4 endocytosis, which involves its dynamic association with β-arrestin and highlights the role of endogenous MIIA as a regulator of CXCR4 internalization and, therefore, the onset of SDF-1α signaling.

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“…Furthermore, cytoplasmic polymeric actin is typically associated with myosin II. Yet there is little evidence for the nuclear presence of myosin II (Obungu et al, 2003), which might also indicate an absence or the formation of a structurally different form of F-actin in the nucleus. However, F-actin, which is capable of phalloidin binding, was recently detected by live-cell imaging in nuclei transplanted into Xenopus oocytes (Miyamoto et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Actin nucleators in the nucleus: an emerging theme

Weston

Coutts

Thangué

2012

Journal of Cell Science

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SummaryActin is an integral component of the cytoskeleton, forming a plethora of macromolecular structures that mediate various cellular functions. The formation of such structures relies on the ability of actin monomers to associate into polymers, and this process is regulated by actin nucleation factors. These factors use monomeric actin pools at specific cellular locations, thereby permitting rapid actin filament formation when required. It has now been established that actin is also present in the nucleus, where it is implicated in chromatin remodelling and the regulation of eukaryotic gene transcription. Notably, the presence of typical actin filaments in the nucleus has not been demonstrated directly. However, studies in recent years have provided evidence for the nuclear localisation of actin nucleation factors that promote cytoplasmic actin polymerisation. Their localisation to the nucleus suggests that these proteins mediate collaboration between the cytoskeleton and the nucleus, which might be dependent on their ability to promote actin polymerisation. The nature of this cooperation remains enigmatic and it will be important to elucidate the physiological relevance of the link between cytoskeletal actin networks and nuclear events. This Commentary explores the current evidence for the nuclear roles of actin nucleation factors. Furthermore, the implication of actin-associated proteins in relaying exogenous signals to the nucleus, particularly in response to cellular stress, will be considered.

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Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain

Cited by 40 publications

References 53 publications

The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors

The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors

Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1α

Actin nucleators in the nucleus: an emerging theme

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