ArticleNucleic acids research2009
FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.Cell death & disease · 2019Article
- The Id-protein family in developmental and cancer-associated pathways.Cell communication and signaling : CCS · 2017Review
- The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription.Cell death & disease · 2016Article
- The Role of Id2 Protein in Neuroblatoma in Children.Pathology oncology research : POR · 2015Article
- Downregulation of Id2 increases chemosensitivity of glioma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.British journal of cancer · 2013Article
- Article
- Cloning, purification and preliminary X-ray data analysis of the human ID2 homodimer.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
- FHL2 binds calcineurin and represses pathological cardiac growth.Molecular and cellular biology · 2012Article
- Bioinformatics analysis of proteomic profiles during the process of anti-Thy1 nephritis.Molecular & cellular proteomics : MCP · 2012Article
- LRP16 integrates into NF-κB transcriptional complex and is required for its functional activation.PloS one · 2011Article
- Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering LRP16 in cytoplasm.BMC cell biology · 2009Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitor of differentiation 2 (Id2) is a natural inhibitor of the basic helix-loop-helix transcription factors. Although Id2 is well known to prevent differentiation and promote cell-cycle progression and tumorigenesis, the molecular events that regulate Id2 activity remain to be investigated. Here, we identified that Four-and-a-half LIM-only protein 2 (FHL2) is a novel functional repressor of Id2. Moreover, we demonstrated that FHL2 can directly interact with all members of the Id family (Id1-4) via an N-terminal loop-helix structure conserved in Id proteins. FHL2 antagonizes the inhibitory effect of Id proteins on basic helix-loop-helix protein E47-mediated transcription, which was abrogated by the deletion mutation of Ids that disrupted their interaction with FHL2. We also showed a competitive nature between FHL2 and E47 for binding Id2, whereby FHL2 prevents the formation of the Id2-E47 heterodimer, thus releasing E47 to DNA and restoring its transcriptional activity. FHL2 expression was remarkably up-regulated during retinoic acid-induced differentiation of neuroblastoma cells, during which the expression of Id2 was opposite to that. Ectopic FHL2 expression in neuroblastoma cells markedly reduces the transcriptional and cell-cycle promoting functions of Id2. Altogether, these results indicate that FHL2 is an important repressor of the oncogenic activity of Id2 in neuroblastoma cells.
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