Gene Set: LA_MEN1_TARGETS

Standard name LA_MEN1_TARGETS
Systematic name M1182
Brief description Genes up-regulated in cells expressing MEN1 [GeneID=4221].
Full description or abstract Menin is encoded by the tumor suppressor gene MEN1 that is mutated in patients with an inherited tumor syndrome, multiple endocrine neoplasia type 1 (MEN1). Although menin is a nuclear protein and directly binds to DNA through its nuclear localization signals (NLSs), the precise role for each of the NLSs in nuclear translocation and gene expression remains to be elucidated. Here, we show that point mutations in three individual NLSs, NLS1, NLS2, and a novel accessory NLS, NLSa, do not block nuclear translocation, but compromise the ability of menin to repress expression of the endogenous insulin-like growth factor binding protein-2 (IGFBP-2) gene. This repression is not released by an inhibitor of histone deacetylases. Although subtle mutations in menin NLSs do not affect menin association with chromatin, they abolish menin binding to the IGFBP-2 promoter in vivo. Furthermore, each of the NLSs is also crucial for menin-mediated induction of caspase 8 expression. Together, these results suggest that menin may act as a scaffold protein in coordinating activation and repression of gene transcription and that its NLSs play a more important role in controlling gene transcription than merely targeting menin into the nucleus.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16449969   Authors: La P,Desmond A,Hou Z,Silva AC,Schnepp RW,Hua X
Exact source Table 1
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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