Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity

Agostinho, Marta; Santos, Vera Lúcia Pereira dos; Ferreira, Fernando; Costa, Rafael Menezes da; Cardoso, Joana; Pinheiro, Inês; Rino, José Pedro; Jaffray, Ellis; Hay, Ronald T.; Ferreira, João

doi:10.1158/0008-5472.can-07-2092

Cited by 59 publications

(57 citation statements)

References 38 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition of TopoII␣ activity by ICRF-193 treatment has been shown to increase PICH-loaded ultrafine DNA bridges (36). Interestingly, the same inhibitor is known to increase TopoII␣ SUMOylation in mitosis (37). Thus, it is possible that the hyper-SUMOylation of TopoII␣ by contributes to the retention of PICH at ultrafine DNA bridges during anaphase, in addition to the maintenance of catenated DNA via the inhibition of TopoII␣ activity.…”

Section: Discussionmentioning

confidence: 99%

SUMOylation Regulates Polo-like Kinase 1-interacting Checkpoint Helicase (PICH) during Mitosis

Sridharan

Park

Ryu

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Mitotic SUMOylation is critical for faithful chromosome segregation in eukaryotes. Results: PICH (Plk1-interacting checkpoint helicase) is a SUMO-interacting protein and a mitotic SUMO substrate. Conclusion: PICH can be regulated by binding to SUMOylated proteins and through its own SUMOylation at mitotic centromeres. Significance: The regulation of PICH by SUMO interaction and SUMOylation reveals a novel role for mitotic SUMOylation in centromeric chromatin organization.

show abstract

Section: Discussionmentioning

confidence: 99%

SUMOylation Regulates Polo-like Kinase 1-interacting Checkpoint Helicase (PICH) during Mitosis

Sridharan

Park

Ryu

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The family plays an important role in mitotic chromosome structure and centromeric cohesion, which is down-regulated through TOP2 sumoylation (Azuma et al 2003, Dasso 2008). Furthermore, certain genotoxic, oxidative, and heat shock stresses rapidly increased the level of SUMO TOP1 and SUMO TOP2 conjugates (Mao et al 2000, Agostinho et al 2008. A specific role of TOP2A in germ cells has been suggested, but whether the protein's activity in these cells is regulated by sumoylation remains unknown (Cobb et al 1999).…”

Section: Sumo and Stress In Testicular Cellsmentioning

confidence: 99%

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

Shrivastava¹,

Pekar²,

Grosser³

et al. 2010

Reproduction

View full text Add to dashboard Cite

Small ubiquitin-like modifiers (SUMO) proteins have been implicated in cellular stress response in different tissues, but whether sumoylation has a similar role during spermatogenesis is currently unknown. In this study, changes in the levels of both free SUMO isoforms and high-molecular weight (HMW) SUMO conjugates were monitored before and after the induction of different types of cellular stresses. Using cell lines and primary cells freshly isolated from mouse testes, significant changes were detected in the levels of SUMO1 and SUMO2/3 conjugates following short exposure of the cells to heat stress and oxidative stress. While high concentrations of H 2 O 2 caused an increase in protein sumoylation, low concentrations of H 2 O 2 mostly caused protein desumoylation. Immunofluorescence studies localized SUMO to the sites of DNA double-strand breaks in stressed germ cells and during meiotic recombination. To study the effect of oxidative stress in vivo, animals exposed to tobacco smoke for 12 weeks were used. Changes in sumoylation of HMW proteins were consistent with their oxidative damage in the tobacco-exposed mice. Our results are consistent with the important roles of different SUMO isoforms in stress responses in germ cells. Furthermore, this study identified topoisomerase 2 a as one of the targets of sumoylation during normal spermatogenesis and under stress.

show abstract

“…Mechanistic insight into the regulation of mitosis by SUMOylation has been achieved through the identification of SUMOylated proteins. Examples being the modification of Topoisomerase II by SUMO2/3, to localize it to centromeres [10]–[12] or the modification of Nuf2 and BubR1 with SUMO2/3 to act as a scaffold for recruiting CENP-E to kinetochores [13]. Despite the importance of the SUMO pathway in mitotic regulation, a comprehensive characterization of targets at close to physiological conditions has not been performed.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

et al. 2014

View full text Add to dashboard Cite

During mitosis large alterations in cellular structures occur rapidly, which to a large extent is regulated by post-translational modification of proteins. Modification of proteins with the small ubiquitin-related protein SUMO2/3 regulates mitotic progression, but few mitotic targets have been identified so far. To deepen our understanding of SUMO2/3 during this window of the cell cycle, we undertook a comprehensive proteomic characterization of SUMO2/3 modified proteins in mitosis and upon mitotic exit. We developed an efficient tandem affinity purification strategy of SUMO2/3 modified proteins from mitotic cells. Combining this purification strategy with cell synchronization procedures and quantitative mass spectrometry allowed for the mapping of numerous novel targets and their dynamics as cells progressed out of mitosis. This identified RhoGDIα as a major SUMO2/3 modified protein, specifically during mitosis, mediated by the SUMO ligases PIAS2 and PIAS3. Our data provide a rich resource for further exploring the role of SUMO2/3 modifications in mitosis and cell cycle regulation.

show abstract

Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity

Cited by 59 publications

References 38 publications

SUMOylation Regulates Polo-like Kinase 1-interacting Checkpoint Helicase (PICH) during Mitosis

SUMOylation Regulates Polo-like Kinase 1-interacting Checkpoint Helicase (PICH) during Mitosis

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

Contact Info

Product

Resources

About