LATS1

From Wikipedia, the free encyclopedia

LATS, large tumor suppressor, homolog 1 (Drosophila)

Identifiers

LATS1; WARTS; wts

External IDs

OMIM: 603473 MGI: 1333883 HomoloGene: 55843

Gene ontology
Molecular Function:	• nucleotide binding • magnesium ion binding • protein serine/threonine kinase activity • protein binding • ATP binding • transferase activity • protein kinase binding
Cellular Component:	• spindle pole
Biological Process:	• G2/M transition of mitotic cell cycle • sister chromatid segregation • protein amino acid phosphorylation • cell cycle • mitosis • hormone-mediated signaling • regulation of actin filament polymerization • negative regulation of cyclin-dependent protein kinase activity • cell division

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_004690 (mRNA)
NP_004681 (protein)

XM_618738 (mRNA)
XP_618738 (protein)

Location

Chr 6: 150.02 - 150.08 Mb

Chr 10: 7.38 - 7.4 Mb

Pubmed search

[1]

[2]

LATS, large tumor suppressor, homolog 1 (Drosophila), also known as LATS1, is a human gene.^[1]

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.^[1]

[edit] References

^ ^a ^b Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila).

[edit] 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.
Tao W, Zhang S, Turenchalk GS, et al. (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.
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. 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. 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. 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. 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. 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.
Iida S, Hirota T, Morisaki T, et al. (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.
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. 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. 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.