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题名:NF-B links oestrogen receptor signalling and EMT
作者:Derek C. Radisky, Mina J. Bissell
来源:Nature Cell Biology[IF=19.717]. 9, 361 - 363 (01 Apr 2007) News and Views
URL :http://dx.doi.org/10.1038/ncb0407-361
日期:070415
摘要: Derek C. Radisky1 & Mina J. Bissell2

1 Derek C. Radisky is at the Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA. radisky.derek@mayo.edu
2 Mina J. Bissell is at the Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Abstract

The detrimental effects of nuclear factor-kappa B (NF-B) signalling in cancer cells lacking the oestrogen receptor have now become clear, with the demonstration that increased NF-B levels induce expression of Bcl-2 to both suppress apoptosis and induce epithelialCmesenchymal transitions (EMTs).

Article

Originally identified for their role in immune cells, NF-B transcription factors have since been identified in nearly every cell type and have been found to mediate an incredibly diverse range of processes1. NF-B factors are homo- and heterodimeric proteins composed of five homologous subunits: NF-B1, NF-B2, RelA/p65, RelB and c-Rel (Fig. 1). When localized to the nucleus, all the NF-B complexes bind related DNA sequences to regulate gene expression, although each different complex has distinct cell type-specific functions. NF-B complexes are normally retained in the cytoplasm in an inactive state through the action of IBs, NF-B inhibitors. The complex becomes active when IB dissociates, allowing nuclear translocation of NF-B. NF-B is generally activated by either canonical or non-canonical pathways: in the canonical pathway, the IB kinase (IKK) complex phosphorylates IB, leading to its disassociation from NF-B; in the non-canonical pathway, activation of the IKK subunit stimulates proteolytic processing of the p100 isoform of NF-B2 to generate p52, which can bind RelB. NF-B heterodimers composed of RelB and p52 are notable because they show affinity for distinct DNA targets and may activate different genes, although the specific pathways induced by this process have yet to be determined for most cell types. 8ku 1:

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