Negative regulation of Wnt signalling by HMG2L1, a novel NLK‐binding protein

Yamada, Masahiro; Ohkawara, Bisei; Ichimura, Naoya; Hyodo-Miura, Junko; Urushiyama, Seiichi; Shirakabe, Kyoko; Shibuya, H.

doi:10.1046/j.1365-2443.2003.00666.x

Cited by 31 publications

(41 citation statements)

References 43 publications

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“…The minichromosome maintenance (Mcm) proteins are essential for DNA replication, and expression of Mcm proteins implies the potential for cell proliferation. The HMG2L1, APOL6, and RBM9 genes have also been studied with cancer (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees

Camp¹,

Farnham²,

Cannon‐Albright³

2006

Cancer Research

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Chromosome 22q has become recently a region of interest for prostate cancer. We identified previously a logarithm of odds (LOD) of 2.42 at chromosome 22q12.3. Additionally, this region has been noted by eight other studies, with linkage evidence ranging from LOD of 1.50 to 3.57. Here, we do fine mapping and localization of the region using a pedigreespecific recombinant mapping approach in 14 informative, high-risk Utah pedigrees. These 14 pedigrees were chosen because they were either ''linked'' or ''haplotype-sharing'' pedigrees or both. ''Linked'' pedigrees were those with significant pedigree-specific linkage evidence (LOD, >0.588; P < 0.05) to the 22q12.3 region, regardless of the number of prostate cancer cases sharing the segregating haplotype. ''Haplotype-sharing'' pedigrees were those with at least five prostate cancer cases sharing a segregating haplotype in the 22q12.3 region, regardless of the linkage evidence. In each pedigree, the most likely haplotype configuration (in addition to the multipoint LOD graph for linked pedigrees) was used to infer the position of recombinant events and delimit the segregating chromosomal segment in each pedigree. These pedigree-specific chromosomal segments were then overlaid to form a consensus recombinant map across all 14 pedigrees. Using this method, we identified a 881,538-bp interval at 22q12.3, between D22S1265 and D22S277, which is the most likely region that contains the 22q prostate cancer predisposition gene. The unique Utah extended high-risk pedigree resource allows this powerful localization approach in pedigrees with evidence for segregating predisposition to prostate cancer. We are mutation screening candidate genes in this region to identify specific genetic variants segregating in these pedigrees.

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Section: Discussionmentioning

confidence: 99%

Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees

Camp¹,

Farnham²,

Cannon‐Albright³

2006

Cancer Research

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“…Conversely, expression of Axin, one of the molecules that functions to retain ␤-catenin in the complex in the cytoplasm, increased gradually during thymocyte maturation. Also HMG2L1, a nuclear negative regulator of Wnt signaling (22), was expressed at lower levels in the most immature (and also the SP) populations ( Table 1). Levels of adenomatous polyposis coli, Groucho and transcriptional activators Pygopus and Legless͞Bcl9 (7) did not change during thymocyte differentiation (Table 1).…”

Section: Expression Of Intracellular Signaling Molecules Predisposes mentioning

confidence: 99%

Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules

Weerkamp

Baert

Naber

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

106

124

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Wnt signaling is essential for T cell development in the thymus, but the stages in which it occurs and the molecular mechanisms underlying Wnt responsiveness have remained elusive. Here we examined Wnt signaling activity in both human and murine thymocyte populations by determining ␤-catenin levels, Tcf-reporter activation and expression of Wnt-target genes. We demonstrate that Wnt signaling occurs in all thymocyte subsets, including the more mature populations, but most prominently in the double negative (DN) subsets. This differential sensitivity to Wnt signaling was not caused by differences in the presence of Wnts or Wnt receptors, as these appeared to be expressed at comparable levels in all thymocyte subsets. Rather, it can be explained by high expression of activating signaling molecules in DN cells, e.g., ␤-catenin, plakoglobin, and long forms of Tcf-1, and by low levels of inhibitory molecules. By blocking Wnt signaling from the earliest stage onwards using overexpression of Dickkopf, we show that inhibition of the canonical Wnt pathway blocks development at the most immature DN1 stage. Thus, responsiveness to developmental signals can be regulated by differential expression of intracellular mediators rather than by abundance of receptors or ligands.double negative cells ͉ T cell development ͉ ␤-catenin ͉ Dickkopf

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“…Recently, it was shown that Xenopus NLK (xNLK) binds to a novel HMG-domain containing protein HMG2L1, which can inhibit Wnt signaling in several assays (Yamada et al, 2003). In addition, xNLK binds to xSox11, another HMG-box containing transcription factor, and they cooperatively induce neural development in Xenopus (Hyodo-Miura et al, 2002).…”

Section: Nemo May Target Arm For Degradationmentioning

confidence: 99%

Nemo is an inducible antagonist of Wingless signaling duringDrosophilawing development

Zeng

Verheyen

2004

Development

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is suppressed in wing discs ectopically expressing nmo and enhanced cell autonomously in nmo mutant clones. We find that nmo itself is a target of Wg signaling in the imaginal wing disc. nmo expression is induced upon high levels of Wg signaling and can be inhibited by interfering with Wg signaling. Finally, we observe alterations in Arm stabilization upon modulation of Nemo. These observations suggest that the patterning mechanism governed by Wg involves a negative feedback circuit in which Wg induces expression of its own antagonist Nemo.

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Negative regulation of Wnt signalling by HMG2L1, a novel NLK‐binding protein

Abstract: Background : Wnt signalling plays a critical role in

Cited by 31 publications

References 43 publications

Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees

Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees

Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules

Nemo is an inducible antagonist of Wingless signaling duringDrosophilawing development

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