ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation

Uematsu, Keiji; Okumura, Fumihiro; Tonogai, Syunsuke; Akiko, Joo-Okumura; Alemayehu, Dawit Hailu; Nishikimi, Akihiko; Fukui, Yoshihiro; Nakatsukasa, Kunio; Kamura, Takumi

doi:10.1083/jcb.201603062

Cited by 17 publications

(11 citation statements)

References 42 publications

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“…Accompanied by the resumption of meiosis, ASB7 protein appeared to be colocalized with chromosomes (Figure 1). Furthermore, we found that ASB7 depletion resulted in the failure of spindle assembly and chromosome congression in oocytes and aneuploidy generation (Figure 3), similar to the observations in HeLa cells (Uematsu et al, 2016). Kinetochore is a complex structure that establishes the attachment of spindle microtubules to chromosomes and is thus essential for faithful chromosome segregation (Santaguida and Musacchio, 2009).…”

Section: Discussionsupporting

confidence: 80%

“…Altogether, our data support a model where ASB7, likely through the modulation of K-MT interaction, controls SAC signaling, consequently ensuring the proper assembly of meiotic apparatus in mammalian oocytes. Recently, it has been reported that the ASB7 protein regulates mitosis by targeting DDA3 (differential display and activated by p53) through proteasomal degradation (Uematsu et al, 2016). Future investigation is needed to clarify (i) whether this pathway is functional during mouse oocyte maturation and (ii) whether there are any other specific targets mediating the action of ASB7 on meiosis.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacological induction of endoplasmic reticulum stress results in increased expression of ASB7 and simultaneously activates the unfolded protein response (Anasa et al, 2018a). Notably, a recent study has shown that ASB7 controls microtubule aggregation and chromosome stability in HeLa cells (Uematsu et al, 2016). To date, functions of ASB7 protein in meiotic oocytes have not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

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ASB7 Is a Novel Regulator of Cytoskeletal Organization During Oocyte Maturation

Liu

et al. 2020

Front. Cell Dev. Biol.

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Ankyrin repeat and SOCS box (ASB) family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence of variable repeats. To date, the roles of ASB family members remain largely unknown. In the present study, by employing knockdown analysis, we investigated the effects of ASB7 on mouse oocyte meiosis. We show that specific depletion of ASB7 disrupts maturational progression and meiotic apparatus. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are frequently observed in ASB7-abated oocytes. Consistent with this observation, incidence of aneuploidy is increased in these oocytes. Meanwhile, confocal scanning reveals that loss of ASB7 impairs kinetochore-microtubule interaction and provokes the spindle assembly checkpoint during oocyte meiosis. Furthermore, we find a significant reduction of ASB7 protein in oocytes from aged mice. Importantly, increasing ASB7 expression is capable of partially rescuing the maternal age-induced meiotic defects in oocytes. Together, our data identify ASB7 as a novel player in regulating cytoskeletal organization and discover the potential effects of ASB7 on quality control of aging oocytes.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ASB7 Is a Novel Regulator of Cytoskeletal Organization During Oocyte Maturation

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…ASB2 was found to interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes [ 18 ]. ASB7 degrades DDA3 to regulate spindle dynamics and genome integrity [ 19 ]. ASB9 targets ubiquitous mitochondrial creatine kinase (uMtCK) and regulates mitochondrial function [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1

Yang

Wan

et al. 2021

Biology

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Apoptosis is a very important process of cell death controlled by multiple genes during which cells undergo certain events before dying. Apoptosis helps to clean the unnecessary cells and has critical physiological significance. Altered apoptosis results in a disorder of cell death and is associated with many diseases such as neurodegenerative diseases and cancers. Here, we reported that the ankyrin repeat and SOCS box protein 17 (ASB17) was mainly expressed in the testis and promoted apoptosis both in vivo and in vitro. Analyzing ASB17-deficient mice generated by using the CRISPR/Cas9 system, we demonstrated that ASB17 deficiency resulted in the reduction of apoptosis in spermatogenic cells, but it did not affect the development of spermatozoa or normal fertility. Next, in an in vivo model, ASB17 deficiency prevented the apoptosis of spermatogonia induced by etoposide in male mice. We noted that ASB17 promoted apoptosis in a caspase-dependent manner in vitro. Moreover, ASB17 interacted with the members of the BCL2 family, including BCL2, BCLX, BCLW, and MCL1. Interestingly, ASB17 specifically degraded the two anti-apoptotic factors, BCLW and MCL1, in a ubiquitylation-dependent fashion. Collectively, our findings suggested that ASB17 acted as a distinct positive regulator of cell apoptosis.

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“…Upregulation of E3 ubiquitin ligases is a vital mechanism through which ER stress improves degradation of misfolded ER proteins [ 44 , 45 ]. Previously, ASB7 has been reported to play a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3 [ 46 ]. However, the regulation of ASB7 gene in ER stress is not yet explored.…”

Section: Resultsmentioning

confidence: 99%

Identification of ASB7 as ER stress responsive gene through a genome wide in silico screening for genes with ERSE

et al. 2018

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The endoplasmic reticulum (ER) not only performs its basic function of regulating calcium homeostasis, lipid biosynthesis, folding, modifying and transporting proteins but also plays a decisive role in regulating multiple cellular processes ranging from cell growth and differentiation to apoptosis and autophagy. Disturbances in ER homeostasis initiate the unfolded protein response (UPR) implicated in the pathogenesis of many human diseases. Drugging the UPR components for therapeutic interventions has received considerable attention. The purpose of this study is to identify genes that are previously unsuspected to be regulated under ER stress. Because ER stress-inducible gene expression is majorly regulated under ERSE elements, we screened human genome by adopting an in silico approach using ERSE elements (I, II, III) as probes and identified 337 candidate genes. Having knowledge of the importance of E3 ubiquitin ligase in the ERAD machinery; we validated our preliminary search by focusing on one of the hits i.e. ASB7 gene that encodes E3 ubiquitin ligase. In HeLa cells, we found that pharmacological induction of ER stress led to an increase in the expression of ASB7 with simultaneous activation of UPR pathways. Although knockdown of ASB7 expression leads to significant reduction in GRP78 and CHOP mRNA levels, it did not protect cells from ER stress-induced cell death. Also, an up-regulation in the expression of pro-inflammatory genes like TNF-α and IL-1β in ASB7 knockdown cells was observed under ER stress. Collectively, our findings suggest that ASB7 is regulated under ER stress and this study also identifies several other genes that could apparently be regulated under ER stress.

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ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation

Cited by 17 publications

References 42 publications

ASB7 Is a Novel Regulator of Cytoskeletal Organization During Oocyte Maturation

ASB7 Is a Novel Regulator of Cytoskeletal Organization During Oocyte Maturation

E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1

Identification of ASB7 as ER stress responsive gene through a genome wide in silico screening for genes with ERSE

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