TY - JOUR
T1 - The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.
AU - Zhang, Lei
AU - Ren, Fangfang
AU - Zhang, Qing
AU - Chen, Yongbin
AU - Wang, Bing
AU - Jiang, Jin
N1 - Funding Information:
We thank Tao Yue for technical assistance; and Liqun Luo, Steve Cohen, Jessica Treisman, Konrad Basler, Helen Richardson, Bruce Hay, and Hyung don Ryoo, and the Bloomington stock center and the Exelixis Collection at Harvard Medical School for reagents and fly stocks. We thank Keith Wharton for helping with photography. This work is supported by grants from NIH, Leukemia and Lymphoma Society Scholar Program, and Welch Foundation to J.J., and J.J. is a Eugene McDermott Endowed Scholar in Biomedical Science at University of Texas Southwestern.
PY - 2008/3
Y1 - 2008/3
N2 - The Hippo (Hpo) signaling pathway governs cell growth, proliferation, and apoptosis by controlling key regulatory genes that execute these processes; however, the transcription factor of the pathway has remained elusive. Here we provide evidence that the TEAD/TEF family transcription factor Scalloped (Sd) acts together with the coactivator Yorkie (Yki) to regulate Hpo pathway-responsive genes. Sd and Yki form a transcriptional complex whose activity is inhibited by Hpo signaling. Sd overexpression enhances, whereas its inactivation suppresses, tissue overgrowth caused by Yki overexpression or tumor suppressor mutations in the Hpo pathway. Inactivation of Sd diminishes Hpo target gene expression and reduces organ size, whereas a constitutively active Sd promotes tissue overgrowth. Sd promotes Yki nuclear localization, whereas Hpo signaling retains Yki in the cytoplasm by phosphorylating Yki at S168. Finally, Sd recruits Yki to the enhancer of the pathway-responsive gene diap1, suggesting that diap1 is a direct transcriptional target of the Hpo pathway.
AB - The Hippo (Hpo) signaling pathway governs cell growth, proliferation, and apoptosis by controlling key regulatory genes that execute these processes; however, the transcription factor of the pathway has remained elusive. Here we provide evidence that the TEAD/TEF family transcription factor Scalloped (Sd) acts together with the coactivator Yorkie (Yki) to regulate Hpo pathway-responsive genes. Sd and Yki form a transcriptional complex whose activity is inhibited by Hpo signaling. Sd overexpression enhances, whereas its inactivation suppresses, tissue overgrowth caused by Yki overexpression or tumor suppressor mutations in the Hpo pathway. Inactivation of Sd diminishes Hpo target gene expression and reduces organ size, whereas a constitutively active Sd promotes tissue overgrowth. Sd promotes Yki nuclear localization, whereas Hpo signaling retains Yki in the cytoplasm by phosphorylating Yki at S168. Finally, Sd recruits Yki to the enhancer of the pathway-responsive gene diap1, suggesting that diap1 is a direct transcriptional target of the Hpo pathway.
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U2 - 10.1016/j.devcel.2008.01.006
DO - 10.1016/j.devcel.2008.01.006
M3 - Article
C2 - 18258485
AN - SCOPUS:42049120338
SN - 1534-5807
VL - 14
SP - 377
EP - 387
JO - Developmental cell
JF - Developmental cell
IS - 3
ER -