RT Journal Article
SR Electronic
T1 Cytoskeletal regulation of a transcription factor by DNA mimicry
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.30.462597
DO 10.1101/2021.09.30.462597
A1 Farah Haque
A1 Christian Freniere
A1 Qiong Ye
A1 Nandini Mani
A1 Elizabeth M. Wilson-Kubalek
A1 Pei-I Ku
A1 Ronald A. Milligan
A1 Radhika Subramanian
YR 2021
UL http://biorxiv.org/content/early/2021/09/30/2021.09.30.462597.abstract
AB A long-established strategy for transcription regulation is the tethering of transcription factors to cellular membranes. In contrast, the principal effectors of Hedgehog signaling, the Gli transcription factors, are regulated by microtubules in the primary cilium and the cytoplasm. How Gli is tethered to microtubules remains unclear. We uncover DNA mimicry by the ciliary kinesin Kif7 as a mechanism for the recruitment of Gli to microtubules, revealing a new mode of tethering a DNA-binding protein to the cytoskeleton. Gli increases the Kif7-microtubule affinity and consequently modulates the localization of both proteins to microtubules and the cilium tip. Thus, the kinesin-microtubule system is not a passive Gli tether but a regulatable platform tuned by the kinesin-transcription factor interaction. We re-tooled the unique DNA-mimicry-based Gli-Kif7 interaction for inhibiting the nuclear and cilium localization of Gli. This strategy can be potentially exploited for downregulating erroneously activated Gli in human cancers.Competing Interest StatementThe authors have declared no competing interest.