5b5w

Structural highlights

Function

[MOB1B_MOUSE] Activator of LATS1/2 in the Hippo signaling pathway which 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 STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38L (By similarity). [LATS1_HUMAN] Negative regulator of YAP1 in the Hippo 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 STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function.^{[1] [2] [3] [4] [5] [6]}

See Also

• Serine/threonine protein kinase 3D structures

References

1. ↑ Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S, Makino K, Yamamoto H, Hiraoka T, Kitamura N, Saya H. A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis. FEBS Lett. 1999 Oct 8;459(2):159-65. PMID:10518011
2. ↑ Hirota T, Morisaki T, Nishiyama Y, Marumoto T, Tada K, Hara T, Masuko N, Inagaki M, Hatakeyama K, Saya H. Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. J Cell Biol. 2000 May 29;149(5):1073-86. PMID:10831611
3. ↑ Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H. Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function. Oncogene. 2004 Jul 8;23(31):5266-74. PMID:15122335 doi:http://dx.doi.org/10.1038/sj.onc.1207623
4. ↑ Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, Xu T. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat Cell Biol. 2004 Jul;6(7):609-17. Epub 2004 Jun 27. PMID:15220930 doi:http://dx.doi.org/10.1038/ncb1140
5. ↑ Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. 2008 Feb 29;283(9):5496-509. Epub 2007 Dec 24. PMID:18158288 doi:10.1074/jbc.M709037200
6. ↑ Humbert N, Navaratnam N, Augert A, Da Costa M, Martien S, Wang J, Martinez D, Abbadie C, Carling D, de Launoit Y, Gil J, Bernard D. Regulation of ploidy and senescence by the AMPK-related kinase NUAK1. EMBO J. 2010 Jan 20;29(2):376-86. doi: 10.1038/emboj.2009.342. Epub 2009 Nov 19. PMID:19927127 doi:http://dx.doi.org/10.1038/emboj.2009.342
7. ↑ Kim SY, Tachioka Y, Mori T, Hakoshima T. Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway. Sci Rep. 2016 Jun 23;6:28488. doi: 10.1038/srep28488. PMID:27335147 doi:http://dx.doi.org/10.1038/srep28488