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Kinesins Modify ERR1-Dependent Transcription Using a Conserved Nuclear Receptor Box Motif
A M Pramodh Bandara Seneviratne1,2, Sarah Lidagoster1, Sofia Valbuena-Castor1
1CUNY School of Medicine, City College of New York, New York, NY 10031, USA.
International Journal of Molecular Sciences
|February 25, 2023
Summary
Kinesin motors regulate transcription. The kinesin-3 motor KIF1B binds estrogen related receptor alpha (ERR1) via an LxxLL motif, inhibiting ERR1-mediated transcription and suggesting expanded roles for kinesins in nuclear receptor regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Kinesin motors are microtubule-dependent ATPases involved in intracellular transport and cell division.
- Some kinesins regulate transcription by interacting with nuclear receptors or DNA.
- The LxxLL nuclear receptor box motif in kinesin KIF17 mediates binding to estrogen related receptor alpha (ERR1), suppressing its transcription.
Purpose of the Study:
- To investigate the effects of kinesins with LxxLL motifs on ERR1-mediated transcription.
- To determine if other kinesin motors, besides KIF17, regulate ERR1.
Main Methods:
- Analysis of kinesin family proteins for LxxLL motifs.
- Biochemical assays to test binding between KIF1B and ERR1.
- Functional assays to assess the impact of KIF1B on ERR1-dependent transcription and nuclear entry.
Main Results:
- Kinesin-3 motor KIF1B contains two LxxLL motifs, with one binding to ERR1.
- Expression of a KIF1B fragment with an LxxLL motif inhibits ERR1-dependent transcription.
- KIF1B regulates ERR1 nuclear entry through a mechanism distinct from KIF17.
Conclusions:
- Kinesin KIF1B directly interacts with ERR1 and modulates its transcriptional activity.
- Kinesins play a broader role in nuclear receptor-mediated transcriptional regulation than previously understood.
- The LxxLL motif is a key functional domain for kinesin-nuclear receptor interactions in transcriptional control.
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