Protein-coding gene in the species Homo sapiens
Large tumor suppressor kinase 1 (LATS1) is anenzyme that in humans is encoded by theLATS1 gene .[ 5] [ 6] [ 7]
It has been associated with theHippo signaling pathway , where it phosphorylates YAP andTAZ to inactivate their function.[ 8]
The protein encoded by this gene is a putativeserine/threonine kinase that localizes to themitotic apparatus and complexes withcell cycle controllerCDC2 kinase in earlymitosis . The protein isphosphorylated in a cell-cycle dependent manner, with lateprophase phosphorylation remaining throughmetaphase . TheN-terminal region of the protein binds CDC2 to form a complex showing reducedhistone H1 kinase activity, indicating a role as a negative regulator of CDC2/cyclin A . In addition, theC-terminal kinase domain binds to its own N-terminal region, suggesting potentialnegative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as atumor suppressor . This is supported by studies in knockout mice showing development ofsoft-tissue sarcomas ,ovarian stromal cell tumors and a high sensitivity tocarcinogenic treatments.[ 7]
LATS1 has been shown tointeract withZyxin [ 9] Cdk1 .[ 5]
^a b c GRCh38: Ensembl release 89: ENSG00000131023 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000040021 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^a b 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 . ^ 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 . ^a b "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)" .^ 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 . ^ 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 . 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 .
Activity Regulation Classification Kinetics Types
