SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres.
Sci Rep
; 10(1): 15653, 2020 09 24.
Article
in En
| MEDLINE
| ID: mdl-32973131
ABSTRACT
During mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Centromere
/
Protein Serine-Threonine Kinases
/
Feedback, Physiological
/
TATA-Binding Protein Associated Factors
/
Transcription Factor TFIID
/
DNA-Binding Proteins
/
Histone Acetyltransferases
/
Histone Chaperones
/
Aurora Kinase B
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
Japan