6bn1

Structural highlights

Function

[HIPPO_DROME] Plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein Hippo (Hpo), in complex with its regulatory protein Salvador (Sav), phosphorylates and activates Warts (Wts) in complex with its regulatory protein Mats, which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling pathway inhibits the activity of the transcriptional complex formed by Scalloped (sd) and Yki and the target genes of this pathway include cyclin-E (cycE), diap1 and bantam. Phosphorylates Sav, Wts and Th/DIAP1. Regulates the level of Th/DIAP1 apoptosis inhibitor.^{[1] [2] [3] [4] [5]} [SAV_DROME] Plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein Hippo (Hpo), in complex with its regulatory protein Salvador (Sav), phosphorylates and activates Warts (Wts) in complex with its regulatory protein Mats, which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling pathway inhibits the activity of the transcriptional complex formed by Scalloped (sd) and Yki and the target genes of this pathway include cyclin-E (cycE), diap1 and bantam. Required for cell cycle exit in eye imaginal disk and hid-induced apoptotic cell deaths that are part of normal retinal development. Activation of Drice in eye imaginal disk by either Hid or Rpr is almost completely blocked by Sav expression.^{[6] [7] [8]}

References

1. ↑ Wu S, Huang J, Dong J, Pan D. hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell. 2003 Aug 22;114(4):445-56. PMID:12941273
2. ↑ Harvey KF, Pfleger CM, Hariharan IK. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003 Aug 22;114(4):457-67. PMID:12941274
3. ↑ Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol. 2003 Oct;5(10):914-20. doi: 10.1038/ncb1050. Epub 2003 Sep 21. PMID:14502294 doi:http://dx.doi.org/10.1038/ncb1050
4. ↑ Pantalacci S, Tapon N, Leopold P. The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat Cell Biol. 2003 Oct;5(10):921-7. Epub 2003 Sep 21. PMID:14502295 doi:http://dx.doi.org/10.1038/ncb1051
5. ↑ Jia J, Zhang W, Wang B, Trinko R, Jiang J. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes Dev. 2003 Oct 15;17(20):2514-9. PMID:14561774 doi:http://dx.doi.org/10.1101/gad.1134003
6. ↑ Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber D, Hariharan IK. salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell. 2002 Aug 23;110(4):467-78. PMID:12202036
7. ↑ Kango-Singh M, Nolo R, Tao C, Verstreken P, Hiesinger PR, Bellen HJ, Halder G. Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila. Development. 2002 Dec;129(24):5719-30. PMID:12421711
8. ↑ Harvey KF, Pfleger CM, Hariharan IK. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003 Aug 22;114(4):457-67. PMID:12941274