TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation

M. T. Epping, A. Lunardi, D. Nachmani, M. Castillo-Martin, T. H. Thin, C. Cordon-Cardo, P. P. Pandolfi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

REST/NRSF is a transcriptional repressor of neuronal genes that has been implicated in development and cancer. In epithelial tissues, REST acts as a tumor suppressor and in breast cancer, loss of REST is associated with disease recurrence and poor prognosis. Here, we identify TSPYL2 (also known as CDA1 and DENTT) as a novel component of the REST protein complex. We show that REST and TSPYL2 are regulators of TGFβ signaling and that cell-cycle arrest induced by TGFβ requires both REST and TSPYL2. Importantly, knockdown of REST or TSPYL2 resulted in transformation of human mammary epithelial cells. Mechanistically, we demonstrate that the TSPYL2/REST complex promotes TGFβ signaling by repressing the expression of genes, such as the proto-oncogene neurotrophic tyrosine kinase receptor C (TrkC). These data provide insight into the role of RESTas a tumor suppressor in epithelial tissues through the regulation of the TGFβ pathway.

Original languageAmerican English
Pages (from-to)1353-1362
Number of pages10
JournalCell Death and Differentiation
Volume22
Issue number8
DOIs
StatePublished - 7 Aug 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

Fingerprint

Dive into the research topics of 'TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation'. Together they form a unique fingerprint.

Cite this