724C Poster - 11. Cell division and cell growth
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jung-Wan Mok ^1,2; Kwang-Wook Choi ¹

Affiliations:
1) KAIST (Korea Advanced Institute of Science & Technology), Daejeon, South Korea; 2) Department of Molecular and Human genetics, Baylor College of Medicine, Houston, TX

Keywords:
w. Hippo signaling; q. developmental modulation

Proper regulation of cell proliferation and cell death is essential for tissue homeostasis and organ growth in developing animals. Multiple evolutionarily conserved signaling pathways regulate the growth of tissues and organs. Hippo signaling is a conserved mechanism for controlling organ growth. Increasing evidence suggests that Hippo signaling is modulated by various cellular factors for normal development and tumorigenesis. Hence, identification of these factors is pivotal for understanding the mechanism for the regulation of Hippo signaling. Drosophila Mnat9 is a putative N-acetyltransferase that is required for cell survival by affecting JNK signaling. Here we show that Mnat9 is involved in the negative regulation of Hippo signaling. RNAi knockdown of Mnat9 in the eye disc suppresses the rough eye phenotype of overexpressing Crumbs (Crb), an upstream factor of the Hippo pathway. Conversely, Mnat9 RNAi enhances the eye phenotype caused by overexpressing Expanded (Ex) or Warts (Wts) that acts downstream to Crb. Similar genetic interactions between Mnat9 and Hippo pathway genes are found in the wing. The reduced wing phenotype of Mnat9 RNAi is suppressed by overexpression of Yorkie (Yki), while it is suppressed by knockdown of Hippo upstream factors like Ex, Merlin, or Kibra. Mnat9 co-immunoprecipitates with Mer, implying their function in a protein complex. Furthermore, Mnat9 overexpression together with Hpo knockdown causes tumorous overgrowth in the abdomen. Our data suggest that Mnat9 is required for organ growth and can induce tumorous growth by negatively regulating the Hippo signaling pathway. It has been suggested that Mnat9 functions in developing Drosophila are evolutionarily conserved since loss-of-function phenotypes of Mnat9 can be effectively rescued by expressing human homolog protein hNAT9. Our data also indicate that Mnat9 and hNAT9 share similar features in inducing tumor growth through Hippo signaling interaction. As the biological function of hNAT9 in humans are currently unknown, these results are expected to provide essential information on the role of hNAT9 in humans and how it relates to the Hippo signaling pathway.