TY - JOUR
T1 - Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease
AU - Mishra-Gorur, Ketu
AU - Barak, Tanyeri
AU - Kaulen, Leon D.
AU - Henegariu, Octavian
AU - Jin, Sheng Chih
AU - Aguilera, Stephanie Marie
AU - Yalbir, Ezgi
AU - Goles, Gizem
AU - Nishimura, Sayoko
AU - Miyagishima, Danielle
AU - Djenoune, Lydia
AU - Altinok, Selin
AU - Rai, Devendra K.
AU - Viviano, Stephen
AU - Prendergast, Andrew
AU - Zerillo, Cynthia
AU - Ozcan, Kent
AU - Baran, Burcin
AU - Sencar, Leman
AU - Goc, Nukte
AU - Yarman, Yanki
AU - Ercan-Sencicek, A. Gulhan
AU - Bilguvar, Kaya
AU - Lifton, Richard P.
AU - Moliterno, Jennifer
AU - Louvi, Angeliki
AU - Yuan, Shiaulou
AU - Deniz, Engin
AU - Brueckner, Martina
AU - Gunel, Murat
N1 - Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
PY - 2023/4/18
Y1 - 2023/4/18
N2 - While somatic variants of TRAF7 (Tumor necrosis factor receptor-associated factor 7) underlie anterior skull-base meningiomas, here we report the inherited mutations of TRAF7 that cause congenital heart defects. We show that TRAF7 mutants operate in a dominant manner, inhibiting protein function via heterodimerization with wild-type protein. Further, the shared genetics of the two disparate pathologies can be traced to the common origin of forebrain meninges and cardiac outflow tract from the TRAF7-expressing neural crest. Somatic and inherited mutations disrupt TRAF7-IFT57 interactions leading to cilia degradation. TRAF7-mutant meningioma primary cultures lack cilia, and TRAF7 knockdown causes cardiac, craniofacial, and ciliary defects in Xenopus and zebrafish, suggesting a mechanistic convergence for TRAF7-driven meningiomas and developmental heart defects.
AB - While somatic variants of TRAF7 (Tumor necrosis factor receptor-associated factor 7) underlie anterior skull-base meningiomas, here we report the inherited mutations of TRAF7 that cause congenital heart defects. We show that TRAF7 mutants operate in a dominant manner, inhibiting protein function via heterodimerization with wild-type protein. Further, the shared genetics of the two disparate pathologies can be traced to the common origin of forebrain meninges and cardiac outflow tract from the TRAF7-expressing neural crest. Somatic and inherited mutations disrupt TRAF7-IFT57 interactions leading to cilia degradation. TRAF7-mutant meningioma primary cultures lack cilia, and TRAF7 knockdown causes cardiac, craniofacial, and ciliary defects in Xenopus and zebrafish, suggesting a mechanistic convergence for TRAF7-driven meningiomas and developmental heart defects.
KW - TRAF7
KW - cilia
KW - congenital heart defect
KW - meningioma
UR - https://www.scopus.com/pages/publications/85152482360
U2 - 10.1073/pnas.2214997120
DO - 10.1073/pnas.2214997120
M3 - Article
C2 - 37043537
AN - SCOPUS:85152482360
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
M1 - e2214997120
ER -