TY - JOUR
T1 - TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation
AU - Epping, M. T.
AU - Lunardi, A.
AU - Nachmani, D.
AU - Castillo-Martin, M.
AU - Thin, T. H.
AU - Cordon-Cardo, C.
AU - Pandolfi, P. P.
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84935687993&partnerID=8YFLogxK
U2 - 10.1038/cdd.2014.226
DO - 10.1038/cdd.2014.226
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C2 - 25613376
AN - SCOPUS:84935687993
SN - 1350-9047
VL - 22
SP - 1353
EP - 1362
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 8
ER -
