Biology:LATS1
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Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene.[1][2][3]
It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function.[4]
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.[3]
Interactions
LATS1 has been shown to interact with Zyxin[5] and Cdk1.[1]
References
- ↑ 1.0 1.1 "Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity". Nat Genet 21 (2): 177–81. February 1999. doi:10.1038/5960. PMID 9988268.
- ↑ "Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function". Oncogene 23 (31): 5266–74. July 2004. doi:10.1038/sj.onc.1207623. PMID 15122335.
- ↑ 3.0 3.1 "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9113.
- ↑ "Tumor suppressor LATS1 is a negative regulator of oncogene YAP". J. Biol. Chem. 283 (9): 5496–509. February 2008. doi:10.1074/jbc.M709037200. PMID 18158288.
- ↑ Hirota, T; Morisaki T; Nishiyama Y; Marumoto T; Tada K; Hara T; Masuko N; Inagaki M et al. (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. PMID 10831611.
Further reading
- "Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase.". Development 121 (4): 1053–63. 1995. doi:10.1242/dev.121.4.1053. PMID 7743921.
- "Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.". Nat. Genet. 21 (2): 182–6. 1999. doi:10.1038/5965. PMID 9988269.
- "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. 1999. doi:10.1016/S0014-5793(99)01224-7. PMID 10518011.
- "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. 2000. doi:10.1083/jcb.149.5.1073. PMID 10831611.
- "WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis.". FEBS Lett. 529 (2–3): 319–24. 2002. doi:10.1016/S0014-5793(02)03360-4. PMID 12372621.
- "Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma". Lab. Invest. 82 (10): 1427–35. 2002. doi:10.1097/01.lab.0000032381.68634.ca. PMID 12379777.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "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. 2003. doi:10.1074/jbc.M211974200. PMID 12624101.
- "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. 2004. doi:10.1021/ac035352d. PMID 15144186.
- "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1". Nat. Cell Biol. 6 (7): 609–17. 2004. doi:10.1038/ncb1140. PMID 15220930.
- "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene 24 (12): 2076–86. 2005. doi:10.1038/sj.onc.1208445. PMID 15688006.
- "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. 2005. doi:10.1158/1078-0432.CCR-04-1773. PMID 15746036.
- "The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death". Oncogene 24 (34): 5287–98. 2005. doi:10.1038/sj.onc.1208682. PMID 16007220.
- "Human LATS1 is a mitotic exit network kinase". Cancer Res. 65 (15): 6568–75. 2005. doi:10.1158/0008-5472.CAN-05-0862. PMID 16061636.
- "Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma". Neurosci. Res. 56 (4): 450–8. 2007. doi:10.1016/j.neures.2006.09.006. PMID 17049657.
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