Mitotic activity of survivin is regulated by acetylation at K129

Aljaberi, Aysha M.; Webster, Jamie; Wheatley, Sally P.

doi:10.1080/15384101.2015.1033597

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…We found that OBP-801 treatment of dividing RMS cells induced γH2AX-positive aberrant metaphase morphologies, concurrent with lower levels and misalignment of survivin. Recently, Aljaberi et al reported that the activity of survivin in mitosis was regulated by cyclical acetylation and deacetylation during mitosis (33), which may explain how an HDAC inhibitor could induce mitotic arrest via survivin in a manner consistent with our results. These results indicated that OBP-801 may induce apoptosis in RMS cells via mitotic catastrophe.…”

Section: Discussionsupporting

confidence: 89%

OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells

et al. 2018

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Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer of musculoskeletal origin. Despite multidisciplinary approaches, such as surgical resection, irradiation, and intensive chemotherapy, adopted for its treatment, the prognosis of patients with high-risk RMS remains poor. Thus, molecularly targeted therapies are required to improve patient survival and minimize side effects. Histone deacetylases (HDACs) modify transcription by deacetylation of the lysine residues in chromatin histone tails and several non-histone proteins. HDAC inhibitors, classes of compounds targeted to various HDAC proteins, are being studied for their roles in several types of cancers in a rigorous manner. This study aimed to investigate the potential of a novel HDAC inhibitor, OBP-801, as a therapeutic agent for the treatment of RMS. We used 8 RMS cell lines in this study. Protein expression patterns, cell proliferation, cell cycle status, and apoptosis in RMS cells after OBP-801 treatment in vitro were investigated. We also studied the antitumor activity of OBP-801 in an in vivo xenograft mouse model. We observed cell cycle arrest at the M-phase and apoptosis in all RMS cell lines after exposure to pharmacological levels of OBP-801 for 24 h. Immunofluorescence staining revealed that OBP-801 may induce mitotic catastrophe via chromosome misalignment and reduced survivin expression, ultimately leading to apoptosis. Our results demonstrated that the novel HDAC inhibitor OBP-801 was an effective inhibitor of RMS cell line proliferation and may be a potent therapeutic option for RMS.

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Section: Discussionsupporting

confidence: 89%

OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells

et al. 2018

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“…Survivin plays an important role in the regulation of mitosis [ 30 , 33 ]. It is expressed in a cell cycle dependent manner as reported mostly in G2-M phase [ 34 ].…”

Section: Survivinmentioning

confidence: 99%

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

Khan

Yadav

et al. 2017

Cell Mol Biol Lett

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Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.

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“…Survivin is essential for targeting the CPC to the centromere during mitosis (Kelly et al, 2010;Wang et al, 2010;Yamagishi et al, 2010), and it undergoes phosphorylation and acetylation, which affect its functions (Aljaberi et al, 2015;Barrett et al, 2011Barrett et al, , 2009Colnaghi and Wheatley, 2010;O'Connor et al, 2000;Wheatley et al, 2007Wheatley et al, , 2004. It is not fully understood, however, how these modifications regulate the activity of survivin during mitosis.…”

Section: Introductionmentioning

confidence: 99%

A direct interaction between survivin and myosin II is required for cytokinesis

Babkoff¹,

Cohen-Kfir²,

Aharon³

et al. 2019

Journal of Cell Science

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An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), composed of Aurora-B kinase, INCENP, borealin and survivin (also known as BIRC5), regulates various processes during mitosis, including cytokinesis. It is not understood, however, how CPC regulates cytokinesis. We show that survivin binds to non-muscle myosin II (NMII), regulating its filament assembly. Survivin and NMII interact mainly in telophase, and Cdk1 regulates their interaction in a mitotic-phase-specific manner, revealing the mechanism for the specific timing of survivin-NMII interaction during mitosis. The survivin-NMII interaction is indispensable for cytokinesis, and its disruption leads to multiple mitotic defects. We further show that only the survivin homodimer binds to NMII, attesting to the biological importance for survivin homodimerization. We suggest a novel function for survivin in regulating the spatio-temporal formation of the acto-NMII contractile ring during cytokinesis and we elucidate the role of Cdk1 in regulating this process. This article has an associated First Person interview with the first author of the paper.

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Mitotic activity of survivin is regulated by acetylation at K129

Cited by 8 publications

References 32 publications

OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells

OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

A direct interaction between survivin and myosin II is required for cytokinesis

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