Table 2.

Transcriptional activation of c-myc and other genes by NDPK/Nm23/Awd

Features:
• In 1993, Postel et al. (1993) identified NDPK-B/Nm23-H2 as the PuF transcription factor binding the nuclease hypersensitive element (NHE) at positions –142 to –115 of the c-myc promoter.
• DNA binding and transactivational activities were maintained in a NDPK catalytically inactive Nm23-H2 H118F mutant (Postel and Ferrone, 1994). Other amino acids in NDPK (Arg 34, Asn-69, Lys 135),all charged, were identified as importantto DNA binding (Postel et al. 1996).
• NDPKs A and B/Nm23–H1 and –H2 were reported to repress the transcriptional activity of the pdgf promoter (Cervoni et al. 2003).
• The c-myc NHE was reported to form a G-quadraplex structure which suppresses c-myc transcription. NDPK-B/Nm23-H2 was postulated to remodel this structure, either by an intrinsic DNA endonuclease activity or by DNA unwinding (Postel et al. 2000a).
Concerns:
• For the identification of the c-myc promoter transcriptional activity, bacterially produced NDPK-B/Nm23-H2 was only demonstrated to be pure on Coomassie stained gels (Postel et al. 1993).
• NDPK-B/Nm23-H2 bound to both single stranded and duplex portions of the c-myc NHE (Postel et al. 2000b, Postel et al. 2002). NDPK/Nm23 proteins bound to single stranded DNA in a non-sequence specific manner (Hildebrandt et al. 1995, Agou et al. 1999).
• Nm23-H2 did not function as a c-myc transcription factor using multiple promoter activity constructs (Michelotti et al. 1997, Chae et al. 1998).
• The c-myc expression of control and Nm23 transfected cell lines was unchanged.
• A manuscript describing the interaction of NDPK/Nm23 with a c-myc quadraplex structure was retracted (Grand et al. 2004).
• Further purification of recombinant NDPK/Nm23 resulted in a separation of the DNA nuclease activity from the protein, implying a contaminant (Dexheimer et al. 2009).