Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene.
It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function.
The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced histone H1 kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments.
Interactions
LATS1 has been shown to interact with Zyxin6 and Cdk1.7
Further reading
- Xu T, Wang W, Zhang S, et al. (1995). "Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase". Development. 121 (4): 1053–63. doi:10.1242/dev.121.4.1053. PMID 7743921.
- St John MA, Tao W, Fei X, et al. (1999). "Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction". Nat. Genet. 21 (2): 182–6. doi:10.1038/5965. PMID 9988269. S2CID 11882936.
- Nishiyama Y, Hirota T, Morisaki T, et al. (1999). "A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis". FEBS Lett. 459 (2): 159–65. doi:10.1016/S0014-5793(99)01224-7. PMID 10518011. S2CID 22292346.
- Hirota T, Morisaki T, Nishiyama Y, et al. (2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. PMC 2174824. PMID 10831611.
- Morisaki T, Hirota T, Iida S, et al. (2002). "WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis". FEBS Lett. 529 (2–3): 319–24. doi:10.1016/S0014-5793(02)03360-4. PMID 12372621. S2CID 45272429.
- Hisaoka M, Tanaka A, Hashimoto H (2002). "Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma". Lab. Invest. 82 (10): 1427–35. doi:10.1097/01.lab.0000032381.68634.ca. PMID 12379777. S2CID 34100799.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T (2003). "Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor". J. Biol. Chem. 278 (20): 17609–14. doi:10.1074/jbc.M211974200. hdl:2433/148480. PMID 12624101.
- Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
- Yang X, Yu K, Hao Y, et al. (2004). "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1". Nat. Cell Biol. 6 (7): 609–17. doi:10.1038/ncb1140. PMID 15220930. S2CID 20493738.
- Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Chan EH, Nousiainen M, Chalamalasetty RB, et al. (2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076–86. doi:10.1038/sj.onc.1208445. PMID 15688006. S2CID 27285160.
- Takahashi Y, Miyoshi Y, Takahata C, et al. (2005). "Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers". Clin. Cancer Res. 11 (4): 1380–5. doi:10.1158/1078-0432.CCR-04-1773. PMID 15746036. S2CID 23415582.
- Kuninaka S, Nomura M, Hirota T, et al. (2005). "The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death". Oncogene. 24 (34): 5287–98. doi:10.1038/sj.onc.1208682. PMID 16007220. S2CID 25678521.
- Bothos J, Tuttle RL, Ottey M, et al. (2005). "Human LATS1 is a mitotic exit network kinase". Cancer Res. 65 (15): 6568–75. doi:10.1158/0008-5472.CAN-05-0862. PMID 16061636.
- Jiang Z, Li X, Hu J, et al. (2007). "Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma". Neurosci. Res. 56 (4): 450–8. doi:10.1016/j.neures.2006.09.006. PMID 17049657. S2CID 22763208.
References
Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T (February 1999). "Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity". Nat Genet. 21 (2): 177–81. doi:10.1038/5960. PMID 9988268. S2CID 32090556. /wiki/Doi_(identifier) ↩
Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H (July 2004). "Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function". Oncogene. 23 (31): 5266–74. doi:10.1038/sj.onc.1207623. PMID 15122335. S2CID 25545351. /wiki/Doi_(identifier) ↩
"Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9113 ↩
Hao Y, Chun A, Cheung K, Rashidi B, Yang X (February 2008). "Tumor suppressor LATS1 is a negative regulator of oncogene YAP". J. Biol. Chem. 283 (9): 5496–509. doi:10.1074/jbc.M709037200. PMID 18158288. https://doi.org/10.1074%2Fjbc.M709037200 ↩
"Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9113 ↩
Hirota T, Morisaki T, Nishiyama Y, Marumoto T, Tada K, Hara T, Masuko N, Inagaki M, Hatakeyama K, Saya H (May 2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. ISSN 0021-9525. PMC 2174824. PMID 10831611. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174824 ↩
Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T (February 1999). "Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity". Nat Genet. 21 (2): 177–81. doi:10.1038/5960. PMID 9988268. S2CID 32090556. /wiki/Doi_(identifier) ↩