PUBLICATION
Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease
- Authors
- Mishra-Gorur, K., Barak, T., Kaulen, L.D., Henegariu, O., Jin, S.C., Aguilera, S.M., Yalbir, E., Goles, G., Nishimura, S., Miyagishima, D., Djenoune, L., Altinok, S., Rai, D.K., Viviano, S., Prendergast, A., Zerillo, C., Ozcan, K., Baran, B., Sencar, L., Goc, N., Yarman, Y., Ercan-Sencicek, A.G., Bilguvar, K., Lifton, R.P., Moliterno, J., Louvi, A., Yuan, S., Deniz, E., Brueckner, M., Gunel, M.
- ID
- ZDB-PUB-230413-50
- Date
- 2023
- Source
- Proceedings of the National Academy of Sciences of the United States of America 120: e2214997120e2214997120 (Journal)
- Registered Authors
- Keywords
- TRAF7, cilia, congenital heart defect, meningioma
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- Heart Defects, Congenital*/genetics
- Humans
- Meningeal Neoplasms*/genetics
- Meningioma*/genetics
- Meningioma*/pathology
- Mutation
- Skull/metabolism
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- PubMed
- 37043537 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Mishra-Gorur, K., Barak, T., Kaulen, L.D., Henegariu, O., Jin, S.C., Aguilera, S.M., Yalbir, E., Goles, G., Nishimura, S., Miyagishima, D., Djenoune, L., Altinok, S., Rai, D.K., Viviano, S., Prendergast, A., Zerillo, C., Ozcan, K., Baran, B., Sencar, L., Goc, N., Yarman, Y., Ercan-Sencicek, A.G., Bilguvar, K., Lifton, R.P., Moliterno, J., Louvi, A., Yuan, S., Deniz, E., Brueckner, M., Gunel, M. (2023) Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease. Proceedings of the National Academy of Sciences of the United States of America. 120:e2214997120e2214997120.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping