TY - JOUR
T1 - ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation
AU - Uematsu, Keiji
AU - Okumura, Fumihiko
AU - Tonogai, Syunsuke
AU - Joo-Okumura, Akiko
AU - Alemayehu, Dawit Hailu
AU - Nishikimi, Akihiko
AU - Fukui, Yoshinori
AU - Nakatsukasa, Kunio
AU - Kamura, Takumi
N1 - Funding Information:
Acknowledgments This work was supported by Japan Society for the Promotion of Science KAKENHI grants 25291023 (to F. Okumura and T. Kamura), 25860043 (to F. Okumura), 24112006 and 15K14474 (to T. Kamura), 25870312 and 15K18503 (to K. Nakatsukasa), and 13J40160 (to A. Joo-Okumura), the Uehara Memorial Foundation (to F. Okumura), and the Inamori Foundation (to F. Okumura).
Publisher Copyright:
© 2016 Uematsu et al.
PY - 2016
Y1 - 2016
N2 - Proper dynamic regulation of the spindle is essential for successful cell division. However, the molecular mechanisms that regulate spindle dynamics in mitosis are not fully understood. In this study, we show that Cullin 5-interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3, a regulator of spindle dynamics, thereby targeting it for proteasomal degradation. The presence of microtubules (MTs) prevented the ASB7-DDA3 interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization and increased the proportion of cells with unaligned chromosomes, and this phenotype was rescued by deletion of DDA3. Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3.
AB - Proper dynamic regulation of the spindle is essential for successful cell division. However, the molecular mechanisms that regulate spindle dynamics in mitosis are not fully understood. In this study, we show that Cullin 5-interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3, a regulator of spindle dynamics, thereby targeting it for proteasomal degradation. The presence of microtubules (MTs) prevented the ASB7-DDA3 interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization and increased the proportion of cells with unaligned chromosomes, and this phenotype was rescued by deletion of DDA3. Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3.
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U2 - 10.1083/jcb.201603062
DO - 10.1083/jcb.201603062
M3 - Article
C2 - 27697924
AN - SCOPUS:84991250600
SN - 0021-9525
VL - 215
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
M1 - 95
ER -