LATS1

LATS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZRK, 5BRK, 5B5W
Identifiers
Aliases	LATS1 , WARTS, wts, large tumor suppressor kinase 1
External IDs	OMIM: 603473; MGI: 1333883; HomoloGene: 55843; GeneCards: LATS1; OMA:LATS1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q25.1 Start 149,658,153 bp [1] End 149,718,105 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 A1 Start 7,556,978 bp [2] End 7,592,224 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in germinal epithelium tibia mucosa of paranasal sinus gingival epithelium epithelium of nasopharynx parietal pleura visceral pleura seminal vesicula retinal pigment epithelium palpebral conjunctiva Top expressed in genital tubercle tail of embryo uterus ganglionic eminence ventricular zone ovary lens jejunum granulocyte ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding protein kinase binding protein kinase activity kinase activity transferase activity metal ion binding magnesium ion binding protein serine/threonine kinase activity ATP binding estrogen receptor binding Cellular component microtubule organizing center spindle pole cytoplasm cytoskeleton cytosol Biological process cell cycle phosphorylation G2/M transition of mitotic cell cycle regulation of actin filament polymerization inner cell mass cell fate commitment keratinocyte differentiation negative regulation of cyclin-dependent protein serine/threonine kinase activity regulation of organ growth regulation of protein-containing complex assembly cytoplasmic sequestering of protein sister chromatid segregation positive regulation of apoptotic process negative regulation of canonical Wnt signaling pathway inner cell mass cellular morphogenesis cell division positive regulation of peptidyl-serine phosphorylation hippo signaling protein phosphorylation hormone-mediated signaling pathway regulation of intracellular estrogen receptor signaling pathway mammary gland epithelial cell differentiation regulation of ubiquitin-dependent protein catabolic process mitotic cell cycle G1/S transition of mitotic cell cycle peptidyl-serine phosphorylation intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9113 16798 Ensembl ENSG00000131023 ENSMUSG00000040021 UniProt O95835 Q6PJG3 Q8BYR2 RefSeq (mRNA) NM_001270519 NM_004690 NM_001350339 NM_001350340 NM_001350392 NM_010690 RefSeq (protein) NP_001257448 NP_004681 NP_001337268 NP_001337269 NP_001337321 NP_034820 Location (UCSC) Chr 6: 149.66 – 149.72 Mb Chr 10: 7.56 – 7.59 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene. ^{[5] [6] [7]}

It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function. ^[8]

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. ^[7]

Interactions

LATS1 has been shown to interact with Zyxin ^[9] and Cdk1. ^[5]

References

1. GRCh38: Ensembl release 89: ENSG00000131023 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040021 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)".
8. 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.
9. 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.

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.