High impact information on EID1

• RFP binds to Rb and prevents the degradation of the EID-1 inhibitor of histone acetylation and differentiation [1].
• A pRB variant that can bind to EID1, but not MDM2, stabilizes EID-1 in cells [2].
• EID-1 is rapidly degraded by the proteasome as cells exit the cell cycle [2].
• Thus, EID-1 may act at a nodal point that couples cell cycle exit to the transcriptional activation of genes required for differentiation [2].
• Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity [2].

Biological context of EID1

• Repression of skeletal muscle-restricted genes was mediated by a block to transactivation by MyoD independent of G(1) exit and, surprisingly, was potentiated by a mutation that prevents EID-1 binding to Rb [3].
• Each point mutation of the conserved amino acid residues in pRb-binding motif of RBP21 abolished its specific interaction with pRb [4].
• Identification and expression analysis of C15orf3, a novel gene on chromosome 15q21.1-->q21.2 [5].
• Furthermore, experimental mutagenesis has been exploited to characterize the interactions between SHP and the transcriptional inhibitor EID-1 [6].

Anatomical context of EID1

• Overexpression of EID-1 in skeletal muscle inhibited tissue-specific transcription [3].
• When expressed in HeLa cells as a green fluorescent protein fusion, RBP21 was distributed throughout the cell [4].
• When overexpressed in COS-7 cells, RBP21 could co-immunoprecipitate with pRb [4].
• 3. Northern blot analysis suggested that RBP21 was widely expressed in various human tissues and cancer cell lines [4].
• Here, we describe a third family member designated EID3 that is highly expressed in testis and shows homology to a region of EID1 implicated in binding to CBP/p300 [7].

Associations of EID1 with chemical compounds

• The repression mechanism of SHP involves several actions including competition with coactivators binding on the AF-2 of nuclear receptors and recruitment of transcriptional inhibitors such as EID-1 [6].

Other interactions of EID1

• Ubiquitination of EID-1 requires an intact C-terminal region that is also necessary for stable binding to p300 and pRB, two proteins that bind to the ubiquitin ligase MDM2 [2].
• Recently, an EID-1 (E1A-like inhibitor of differentiation-1) and EID-2 (EID-1-like inhibitor of differentiation-2) were identified [8].
• However, interaction between SHP Delta128-139 and EID-1 was significantly diminished [9].

Analytical, diagnostic and therapeutic context of EID1

• Sequence analysis indicates that RBP21 shares homology with other retinoblastoma-binding proteins in the pRb-binding motif LxCxE at the C-terminal region [4].
• C15orf3 was mapped to chromosome 15q21.1-->q21.2 using the Stanford G3 radiation hybrid panel [5].

References