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LATS1

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{{Short description|Protein-coding gene in the species Homo sapiens}}

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Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene.{{cite journal |vauthors=Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T | title = Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity | journal = Nat Genet | volume = 21 | issue = 2 | pages = 177–81 |date=February 1999 | pmid = 9988268 | doi = 10.1038/5960 | s2cid = 32090556 }}{{cite journal |vauthors=Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H | title = Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function | journal = Oncogene | volume = 23 | issue = 31 | pages = 5266–74 |date=July 2004 | pmid = 15122335 | doi = 10.1038/sj.onc.1207623 | s2cid = 25545351 | doi-access = }}{{cite web | title = Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9113}}

It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function.{{cite journal |vauthors=Hao Y, Chun A, Cheung K, Rashidi B, Yang X |title=Tumor suppressor LATS1 is a negative regulator of oncogene YAP |journal=J. Biol. Chem. |volume=283 |issue=9 |pages=5496–509 |date=February 2008 |pmid=18158288 |doi=10.1074/jbc.M709037200 |doi-access=free }}

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 Zyxin{{cite journal |last=Hirota |first=T |author2=Morisaki T |author3=Nishiyama Y |author4=Marumoto T |author5=Tada K |author6=Hara T |author7=Masuko N |author8=Inagaki M |author9=Hatakeyama K |author10=Saya H |date=May 2000 |title=Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor |journal=J. Cell Biol. |volume=149 |issue=5 |pages=1073–86 | issn = 0021-9525| pmid = 10831611 |pmc=2174824|doi=10.1083/jcb.149.5.1073 }} and Cdk1.

References

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Further reading

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  • {{cite journal |vauthors=Xu T, Wang W, Zhang S, etal |title=Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. |journal=Development |volume=121 |issue= 4 |pages= 1053–63 |year= 1995 |doi=10.1242/dev.121.4.1053 |pmid= 7743921 }}
  • {{cite journal |vauthors=St John MA, Tao W, Fei X, etal |title=Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. |journal=Nat. Genet. |volume=21 |issue= 2 |pages= 182–6 |year= 1999 |pmid= 9988269 |doi= 10.1038/5965 |s2cid=11882936 }}
  • {{cite journal |vauthors=Nishiyama Y, Hirota T, Morisaki T, etal |title=A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis. |journal=FEBS Lett. |volume=459 |issue= 2 |pages= 159–65 |year= 1999 |pmid= 10518011 |doi=10.1016/S0014-5793(99)01224-7 |s2cid=22292346 |doi-access=free }}
  • {{cite journal |vauthors=Hirota T, Morisaki T, Nishiyama Y, etal |title=Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. |journal=J. Cell Biol. |volume=149 |issue= 5 |pages= 1073–86 |year= 2000 |pmid= 10831611 |doi=10.1083/jcb.149.5.1073 | pmc=2174824 }}
  • {{cite journal |vauthors=Morisaki T, Hirota T, Iida S, etal |title=WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis. |journal=FEBS Lett. |volume=529 |issue= 2–3 |pages= 319–24 |year= 2002 |pmid= 12372621 |doi=10.1016/S0014-5793(02)03360-4 |s2cid=45272429 |doi-access= }}
  • {{cite journal |vauthors=Hisaoka M, Tanaka A, Hashimoto H |title=Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma |journal=Lab. Invest. |volume=82 |issue= 10 |pages= 1427–35 |year= 2002 |pmid= 12379777 |doi= 10.1097/01.lab.0000032381.68634.ca|s2cid=34100799 |doi-access=free }}
  • {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
  • {{cite journal |vauthors=Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T |title=Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor |journal=J. Biol. Chem. |volume=278 |issue= 20 |pages= 17609–14 |year= 2003 |pmid= 12624101 |doi= 10.1074/jbc.M211974200 |doi-access= free |hdl= 2433/148480 |hdl-access= free }}
  • {{cite journal |vauthors=Brill LM, Salomon AR, Ficarro SB, etal |title=Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry |journal=Anal. Chem. |volume=76 |issue= 10 |pages= 2763–72 |year= 2004 |pmid= 15144186 |doi= 10.1021/ac035352d }}
  • {{cite journal |vauthors=Yang X, Yu K, Hao Y, etal |title=LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1 |journal=Nat. Cell Biol. |volume=6 |issue= 7 |pages= 609–17 |year= 2004 |pmid= 15220930 |doi= 10.1038/ncb1140 |s2cid=20493738 }}
  • {{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 |bibcode=2004PNAS..10112130B |doi-access=free }}
  • {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
  • {{cite journal |vauthors=Chan EH, Nousiainen M, Chalamalasetty RB, etal |title=The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1 |journal=Oncogene |volume=24 |issue= 12 |pages= 2076–86 |year= 2005 |pmid= 15688006 |doi= 10.1038/sj.onc.1208445 |s2cid=27285160 }}
  • {{cite journal |vauthors=Takahashi Y, Miyoshi Y, Takahata C, etal |title=Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers |journal=Clin. Cancer Res. |volume=11 |issue= 4 |pages= 1380–5 |year= 2005 |pmid= 15746036 |doi= 10.1158/1078-0432.CCR-04-1773 |s2cid=23415582 |doi-access= }}
  • {{cite journal |vauthors=Kuninaka S, Nomura M, Hirota T, etal |title=The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death |journal=Oncogene |volume=24 |issue= 34 |pages= 5287–98 |year= 2005 |pmid= 16007220 |doi= 10.1038/sj.onc.1208682 |s2cid=25678521 |doi-access= }}
  • {{cite journal |vauthors=Bothos J, Tuttle RL, Ottey M, etal |title=Human LATS1 is a mitotic exit network kinase |journal=Cancer Res. |volume=65 |issue= 15 |pages= 6568–75 |year= 2005 |pmid= 16061636 |doi= 10.1158/0008-5472.CAN-05-0862 |doi-access= }}
  • {{cite journal |vauthors=Jiang Z, Li X, Hu J, etal |title=Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma |journal=Neurosci. Res. |volume=56 |issue= 4 |pages= 450–8 |year= 2007 |pmid= 17049657 |doi= 10.1016/j.neures.2006.09.006 |s2cid=22763208 }}

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{{Hippo signaling pathway}}

{{Serine/threonine-specific protein kinases}}

{{Enzymes}}

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Category:EC 2.7.11

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