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LATS1

From Wikipedia, the free encyclopedia

LATS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLATS1, WARTS, wts, large tumor suppressor kinase 1
External IDsOMIM: 603473; MGI: 1333883; HomoloGene: 55843; GeneCards: LATS1; OMA:LATS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 10: 7.56 – 7.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

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

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131023Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040021Ensembl, 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. ^ 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.
  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. ^ a b "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

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