LATS1

Large tumor suppressor kinase 1
Identifiers
Symbols	LATS1 ; WARTS; wts
External IDs	OMIM: 603473 MGI: 1333883 HomoloGene: 55843 ChEMBL: 6167 GeneCards: LATS1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • magnesium ion binding • protein serine/threonine kinase activity • protein binding • ATP binding • protein kinase binding Cellular component • spindle pole • microtubule organizing center • cytosol Biological process • G1/S transition of mitotic cell cycle • G2/M transition of mitotic cell cycle • sister chromatid segregation • protein phosphorylation • mitotic nuclear division • hormone-mediated signaling pathway • keratinocyte differentiation • regulation of actin filament polymerization • positive regulation of peptidyl-serine phosphorylation • hippo signaling • positive regulation of apoptotic process • regulation of protein complex assembly • negative regulation of cyclin-dependent protein serine/threonine kinase activity • regulation of organ growth • cytoplasmic sequestering of protein • cell division • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9113	16798
Ensembl	ENSG00000131023	ENSMUSG00000040021
UniProt	O95835	Q8BYR2
RefSeq (mRNA)	NM_001270519	NM_010690
RefSeq (protein)	NP_001257448	NP_034820
Location (UCSC)	Chr 6: 149.66 – 149.72 Mb	Chr 10: 7.68 – 7.72 Mb
PubMed search

Serine/threonine-protein kinase 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.^[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 H1 histone 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. 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.
2. 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.
3. "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)".
4. 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.
5. 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. (UNITED STATES) 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. ISSN 0021-9525. PMC 2174824. PMID 10831611.

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. 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.
• 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.
• 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.
• 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.
• 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. 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. 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.
• 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. 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.
• 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.
• 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.
• 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.