Disease relevance of Nedd9

• A monoclonal antibody (mAb 7J6) neutralizing poliovirus type 2 (PV2) and poliovirus type 1 (PV1) was obtained after immunization of BALB/c mice with infectious PV2, strain MEF-1 [1].
• Unequivocal evidence on replication of poliovirus type 2 (strains MEF1 and Lansing) in newborn and suckling mice and on poliovirus myocarditis is presented [2].
• Isolation of the small infective particle in adapted MEF1 poliomyelitis. 1957 [3].

High impact information on Nedd9

• Deletion of a putative myocyte-specific enhancer factor 1 (MEF-1) binding site, containing a canonical E-box motif, had no effects on muscle-specific transcription, indicating that this site is not required for the activity of the enhancer [4].
• In contrast to reports involving cotransfection of 10T1/2 cells with plasmids expressing the myogenic determination factor MyoD, we show that the skeletal myocyte activity of multimerized MEF1 sites is 30-fold lower than that of the 206-bp enhancer [5].
• Mutations at three sites have larger effects in muscle than nonmuscle cells; an A/T-rich site mutation has a pronounced effect in both striated muscle types, mutations at the MEF1 (Right E-box) site are relatively specific to expression in skeletal muscle, and mutations at the CArG site are relatively specific to expression in cardiac muscle [5].
• Mannosamine treatment, which down-regulates cell-surface uPAR, decreased MEF-2 migration by 40% without significantly affecting MEF-1 migration [6].
• A myocyte specific protein complex, MEF1, binds the MCK-R site [7].

Biological context of Nedd9

• One sequence located at approximately -940 base pairs corresponds to the motif called MEF1 which has been shown in other muscle genes to bind the myogenic regulatory factors of which MyoD is one example [8].
• This may be due to an 18% nucleotide difference between the MEF-1 and Sabin 2 strains, resulting in 72 amino acid substitutions and leading to antigenic dissimilarity [9].
• These data suggest that bHLH gene expression is not required for the early steps of osteogenesis; moreover, inhibition of bHLH protein binding to a MEF1-type E box might be an integral part of osteogenic commitment [10].

Associations of Nedd9 with chemical compounds

• Promoter-reporter studies also demonstrated inhibition of MEF-1 driven CAT expression by dexamethasone under differentiation-permissive conditions in RI-2J cells [10].
• MEF-1 oligonucleotide, the E-box sequence from the muscle creatine kinase enhancer, demonstrated no changes in binding with nuclear extracts from moderately differentiated (W-20) or relatively mature (ROS 17/2.8) cells under any conditions tested [10].

Other interactions of Nedd9

• However, in poorly differentiated RI-2J cells, which do not express osteogenic markers unless treated with dexamethasone, induction of differentiation was reflected in transient inhibition of binding to MEF-1 [10].

References