Structure, Expression, and Chromosome Mapping of LATS2, a Mammalian Homologue of the Drosophila Tumor Suppressor Gene lats/warts

A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization

“…Lats1-deficient mice develop tumors (St John et al 1999). The gene encoding Lats2, also known as Kpm (Hori et al 2000;Yabuta et al 2000), resides in a chromosomal region that exhibits frequent loss of heterozygosity (LOH) in human cancers (Yabuta et al 2000), consistent with the idea that it, too, is a tumor suppressor. Human Lats2 is a centrosomal protein (Toji et al 2004), and recent work suggests that it plays a role in regulating the formation of the mitotic spindle apparatus (Abe et al 2006).…”

“…However, additional proteins beyond Lats2 might relay microtubule damage and centrosome/mitotic apparatus dysfunction stress signals to p53, and some of the effects of Lats2 may be exerted in a p53-independent manner. Of particular interest is Lats1, which shares 52% overall sequence identity with Lats2, with 85% sequence identity over the kinase domain (Yabuta et al 2000). Lats1 also resides on interphase centrosomes (Nishiyama et al 1999;Hirota et al 2000).…”

Isolation and characterization of sixteen novel p53 response genes

“…This clone is identical to lats 2 (Yabuta et al, 2000), a human homologue of a tumour suppressor gene originally isolated in Drosophila (Xu et al, 1995). Lats 2 shares 68% identity with the Drosophila lats/ warts while lats 1 shares 60%.…”

“…Among these genes are Ponsin SH3/P12/CAP/ FLAF2 (Mandai et al, 1999), CDCrel2b/H5/PNUTL2 , APOBEC-2 (Liao et al, 1999), IgG, cytokeratin 15 (Leube et al, 1988), HGFL/MSP (Han and Degen, 1993), Zap-70 (Chan et al, 1992), lats2 (Yabuta et al, 2000), PIG3 , and eight unknown genes. Amongst the unknown candidates there is one which shares signi®cant homology with chicken CTCF (Klenova et al, 1993), a protein binding to insulator sequences and in so doing attenuates enhancer cross-talk between physically adjacent promoters (Bell et al, 1999).…”

Downregulation of the large tumor suppressor 2 (LATS2/KPM) gene is associated with poor prognosis in acute lymphoblastic leukemia

“…1 Although chromosome aberrations involving 13q12 have been described in a minority (3-6%) of acute lymphoblastic leukemia (ALL) patients and frequently occur as secondary events after relapse, these patients show an extremely poor outcome. 2 DNA methylation is an essential mechanism for the regulation of gene expression in mammalian cells.…”