RT Journal Article
SR Electronic
T1 Direct role of Bardet–Biedl syndrome proteins in transcriptional regulation
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 362
OP 375
DO 10.1242/jcs.089375
VO 125
IS 2
A1 Gascue, Cecilia
A1 Tan, Perciliz L.
A1 Cardenas-Rodriguez, Magdalena
A1 Libisch, Gabriela
A1 Fernandez-Calero, Tamara
A1 Liu, Yangfan P.
A1 Astrada, Soledad
A1 Robello, Carlos
A1 Naya, Hugo
A1 Katsanis, Nicholas
A1 Badano, Jose L.
YR 2012
UL http://jcs.biologists.org/content/125/2/362.abstract
AB Primary cilia are conserved organelles that play crucial roles as mechano- and chemosensors, as well as transducing signaling cascades. Consequently, ciliary dysfunction results in a broad range of phenotypes: the ciliopathies. Bardet–Biedl syndrome (BBS), a model ciliopathy, is caused by mutations in 16 known genes. However, the biochemical functions of the BBS proteins are not fully understood. Here we show that the BBS7 protein (localized in the centrosomes, basal bodies and cilia) probably has a nuclear role by virtue of the presence of a biologically confirmed nuclear export signal. Consistent with this observation, we show that BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its protein levels, probably through a proteasome-mediated mechanism. In addition, our data supports a similar role for other BBS proteins. Importantly, the interaction with this PcG member is biologically relevant because loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo, including several genes that are crucial for development and for cellular and tissue homeostasis. Our data indicate a hitherto unappreciated, direct role for the BBS proteins in transcriptional regulation and potentially expand the mechanistic spectrum that underpins the development of ciliary phenotypes in patients.