Disease relevance of GMEB1

• Transgenic mice expressing a neurospecific GMEB1 had smaller cerebral infarcts and less brain swelling than wild-type mice in response to transient focal ischemia [1].
• Here, we show that the two PIF/GMEB subunits form site-specific DNA-binding heterodimers when co-expressed from recombinant baculoviruses and homodimers when expressed separately [2].
• The glucocorticoid modulatory element binding proteins 1 and 2 (GMEB-1 and GMEB-2) are of interest both for their multiple activities (e.g. modulation of transactivation by the glucocorticoid receptor and initiation of parvovirus replication) and their membership in the emerging family of KDWK proteins [3].

High impact information on GMEB1

• Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1 [4].
• The knockdown of endogenous GMEB1 using RNA interference revealed that cells with decreased GMEB1 expression are more sensitive to stress and undergo accelerated apoptosis [1].
• Glucocorticoid Modulatory Element-binding Protein 1 Binds to Initiator Procaspases and Inhibits Ischemia-induced Apoptosis and Neuronal Injury [1].
• As determined from gel shift assays, GMEB1 and -2 are not restricted to rat liver cells but appear to be ubiquitous [5].
• Here we present the 1.55 A resolution crystal structure of a central portion of GMEB1, encompassing its SAND domain, which shares 80% sequence identity with the GMEB2 SAND domain [6].

Biological context of GMEB1

• The GMEB proteins have intrinsic transactivation ability, but also control the glucocorticoid response via direct binding to the glucocorticoid receptor [6].
• In many of these, the binding site is within 100 nucleotides of the transcriptional start site, indicating that PIF/GMEB may be involved in regulation of these genes [2].
• Binding of all three complexes is extremely sensitive to methylation of the cytosine residues in the invariant CpG half-site core, suggesting a means by which PIF/GMEB binding could be regulated in vivo [2].
• Here, we report the structure/activity relationships of GMEB-2 and compare them to our previous findings for GMEB-1 [7].
• The tissue distribution of each GMEB is not the same and is highest in fetal and developing tissues, consistent with previous suggestions that both homo- and hetero-oligomers may possess biological activity [3].

Anatomical context of GMEB1

• The dual interactions of MURF-1 with titin and GMEB-1 may link myofibril signaling pathways (perhaps including titin's kinase domain) with muscle gene expression [4].

Associations of GMEB1 with chemical compounds

• The glucocorticoid-modulatory element-binding proteins, GMEB1 and GMEB2, are ubiquitous, multifunctional DNA-binding proteins with important roles in the modulation of transcription upon steroid hormone activation [6].
• This protein complex was simultaneously identified as glucocorticoid modulatory element binding protein (GMEB) by its ability to bind to the glucocorticoid modulating element (GME) upstream of the tyrosine transaminase promoter [2].

Analytical, diagnostic and therapeutic context of GMEB1

• Co-immunoprecipitation experiments confirmed the in vivo interaction of HSP27 with hGMEB1 [8].
• Oligonucleotides corresponding to five of these sequences, chosen to represent the range of half-site separations identified by the consensus, were tested for PIF/GMEB binding by mobility shift assay [2].

References