SUMO-2/3 regulates topoisomerase II in mitosis

Azuma, Yoshiaki; Arnaoutov, Alexei; Dasso, Mary

doi:10.1083/jcb.200304088

Cited by 184 publications

(245 citation statements)

References 29 publications

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“…They could result from differences in the stability of Ubc9 protein and/or sumoylated proteins in the different cell types, for instance, as a consequence of different proliferation rates. Strongly proliferating tissues should have a higher turnover of sumoylated proteins, because sumoylation can be subject to cell cycle control (Azuma et al, 2003;Dieckhoff et al, 2004). In addition, because proliferation is linked to tissue growth, the cellular concentration of maternal Ubc9 should drop faster in tissues with high proliferation rates.…”

Section: The Stability Of Ubc9 Protein and The Kinetics Of Phenotype mentioning

confidence: 99%

“…This protein is mutated in its Sumo-acceptor site, diminishing its E2 activity, while leaving its substrate binding capacity unaltered (Azuma et al, 2003). Thereby over expressed protein competes with both maternally supplied and zygotically produced endogenous Ubc9 protein for substrate proteins.…”

Section: Loss Of Maternal and Zygotic Ubc9 Function Leads To Embryonimentioning

confidence: 99%

“…Loss of Rca1 leads to cells with larger nuclei and increased DNA content (Grosskortenhaus and Sprenger, 2002), as described here for ubc9.1 morphants, making APC components or regulators good candidates for Ubc9 targets mediating its effect during mitosis control. Another good candidate is topoisomerase II, which in Xenopus egg extracts has been shown to be sumoylated, while treatment with dominant negative Ubc9 leads to persistent association of topoisomerase with mitotic chromosomes and to a blockage of sister chromatid separation at the metaphase-anaphase transition (Azuma et al, 2003).…”

Section: Loss Of Ubc9 Leads To Compromised Mitosis and Cellular Overgmentioning

confidence: 99%

“…This ubc9.1 expression pattern is in line with a role during cell proliferation in zebrafish larvae and with functional data obtained in other systems. Thus, Ubc9 has been implicated in various aspects of cell cycle control like chromosome condensation and segregation (Tanaka et al, 1999;Azuma et al, 2003) and the regulation of cyclin stability (Seufert et al, 1995;Dieckhoff et al, 2004), as well as in different DNA repair mechanisms (Hardeland et al, 2002;Hoege et al, 2002;Stelter and Ulrich, 2003).…”

Section: Ubc9 Is Expressed In Proliferative Tissuesmentioning

confidence: 99%

“…In particular, the formation of PML (promyelocytic leukemia) nuclear bodies (Muller et al, 1998), and the inactivation of several transcriptional activators like Lef-1 (Sachdev et al, 2001) and Sp3 (Ross et al, 2002;Sapetschnig et al, 2002) via a recruitment to these nuclear compartments have been shown to be sumoylation-dependent (reviewed in Gill, 2003). In addition, protein sumoylation is involved in the regulation of DNA repair (Hardeland et al, 2002;Hoege et al, 2002;Stelter and Ulrich, 2003) and is required for proper chromosome condensation and separation (Hari et al, 2001;Strunnikov et al, 2001;Bachant et al, 2002;Azuma et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Nowak

Hammerschmidt

2006

MBoC

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Many proteins are modified by conjugation with Sumo, a gene-encoded, ubiquitin-related peptide, which is transferred to its target proteins via an enzymatic cascade. A central component of this cascade is the E2-conjugating enzyme Ubc9, which is highly conserved across species. Loss-of-function studies in yeast, nematode, fruit fly, and mouse blastocystes point to multiple roles of Ubc9 during cell cycle regulation, maintenance of nuclear architecture, chromosome segregation, and viability. Here we show that in zebrafish embryos, reduction of Ubc9 activity by expression of a dominant negative version causes widespread apoptosis, similar to the effect described in Ubc9-deficient mice. However, antisense-based knock down of zygotic ubc9 leads to much more specific defects in late proliferating tissues, such as cranial cartilage and eyes. Affected cartilaginous elements are of relatively normal size and shape, but consist of fewer and larger cells.

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Section: The Stability Of Ubc9 Protein and The Kinetics Of Phenotype mentioning

confidence: 99%

Section: Loss Of Maternal and Zygotic Ubc9 Function Leads To Embryonimentioning

confidence: 99%

Section: Loss Of Ubc9 Leads To Compromised Mitosis and Cellular Overgmentioning

confidence: 99%

Section: Ubc9 Is Expressed In Proliferative Tissuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Nowak

Hammerschmidt

2006

MBoC

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Oncocardiology—Past, Present, and Future

Yeh

Chang

2016

JAMA Cardiol

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IMPORTANCE Oncocardiology is a medical discipline that focuses on the identification, prevention, and treatment of cardiovascular complications related to cancer therapy. This discipline has gained interest from the cardiology community in recent years because of a remarkable increase in the number of cancer survivors and the proliferation of new cancer therapies causing cardiovascular complications, such as hypertension, heart failure, vascular complications, and cardiac arrhythmia. In this review, we provide historical perspectives, highlight new discoveries, and speculate on the opportunity created by merging the research interests and clinical practices of cardiology and oncology. OBSERVATIONS The old paradigm of anthracycline cardiotoxic effects is replaced by new insights that anthracycline targets topoisomerase II β to cause DNA double-strand breaks and a profound change in the transcriptome leading to the generation of reactive oxygen species and the development of mitochondriopathy. Prevention of anthracycline cardiotoxic effects should be based on inhibiting or degrading topoisomerase II β. New challenges were posed by the introduction of trastuzumab and tyrosine kinase inhibitors that revolutionized cancer therapy. The on-target cardiotoxic effects of trastuzumab were owing to a prosurvival benefit of Her2 that binds to neuregulin, whereas the off-target effect of multitargeted tyrosine kinase inhibitors may be mediated by disruption of the vascular endothelial growth factor signaling pathway or the stress-induced angiogenesis. Sensitive imaging techniques, such as global strain, and biomarkers have allowed for early detection of cardiotoxic effects. Early treatment with heart failure medications may be beneficial in preventing the development of late cardiotoxic effects. CONCLUSIONS AND RELEVANCE Close collaboration between cardiologists and oncologists is required to meet the demand of an increasing number of cancer survivors. New insights based on mechanistic studies or genetic discoveries will pave the way for better prevention, diagnosis, and treatment of cancer therapy-induced cardiovascular complications.

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Modulating Nrf2 transcription factor activity: Revealing the regulatory mechanisms of antioxidant defenses during hibernation in 13‐lined ground squirrels

Tessier

Breedon

Storey

2021

Cell Biochemistry & Function

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Mammalian hibernators undergo major behavioural, physiological and biochemical changes to survive hypothermia, ischaemia‐reperfusion and finite fuel reserves during days or weeks of continuous torpor. During hibernation, the 13‐lined ground squirrel (Ictidomys tridecemlineatus) undergoes a global suppression of energetically expensive processes such as transcription and translation, while selectively upregulating certain genes/proteins to mitigate torpor‐related damage. Antioxidant defenses are critical for preventing damage caused by reactive oxygen species (ROS) during torpor and arousal, and Nrf2 is a critical regulator of these antioxidant genes. This study analysed the relative protein expression levels of Nrf2, KEAP1, small Mafs (MafF, MafK and MafG) and catalase and the regulation of Nrf2 transcription factors by post‐translational modifications (PTMs) and protein‐protein interactions with a negative regulator (KEAP1) during hibernation. It was found that a significant increase in MafK during late torpor predicated an increase in relative Nrf2 and catalase levels seen in arousal. Additionally, Nrf2‐KEAP1 protein‐protein interactions and Nrf2 PTMs, including serine phosphorylation and lysine acetylation, were responsive to cycles of torpor‐arousal with peak responses occurring during arousal. These peaks seen during arousal correspond to a surge in oxygen consumption, which causes increased ROS production. Thus, these regulatory mechanisms could be important during hibernation because they provide mechanisms for mitigating the deleterious effects of oxidative stress by modifying Nrf2 expression and function in an energetically inexpensive manner.

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SUMO-2/3 regulates topoisomerase II in mitosis

Cited by 184 publications

References 29 publications

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

Oncocardiology—Past, Present, and Future

Modulating Nrf2 transcription factor activity: Revealing the regulatory mechanisms of antioxidant defenses during hibernation in 13‐lined ground squirrels

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