Human proto-oncogene N-myc encodes nuclear proteins that bind DNA.

Abstract

N-myc is a gene whose amplification has been implicated in the genesis of several malignant human tumors. We have identified two proteins with molecular weights of 65,000 and 67,000 encoded by N-myc. The abundance of these proteins in tumor cells was consonant with the extent of amplification of N-myc. The two proteins apparently arose from the same mRNA, were phosphorylated, were exceptionally unstable, were located in the nucleus of cells, and bound to both single- and double-stranded DNA. These properties suggest that the products of N-myc and of the related proto-oncogene c-myc may have similar biochemical functions and that N-myc may be a regulatory gene. Our findings sustain the view that inordinate expression of N-myc may contribute to the genesis of several different human tumors.

In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

“…(b) To show the`general' polyubiquitination of total cell proteins, 100 mg of both IMR32 and SKNSH ALLnL-treated and untreated lysates were electrophoresed and probed with ubiquitin antibody. IMR32 and SKNSH controls are shown in lanes 1 and 3; IMR32 and SKNSH ALLnL-treated samples are in lanes 2 and 4 respectively consistent with values previously obtained by others (Ikegaki et al, 1986;Slamon et al, 1986;Ramsay et al, 1986). In contrast, the half-life of N-myc was 68 min in the presence of ALLnL ( Figure 5, open triangles).…”

“…N-myc, as are many other proto-oncogene products, is a very short-lived protein with a half-life between 30 and 50 min, as determined in several N-myc ampli®ed neuroblastoma cell lines (Ikegaki et al, 1986;Slamon et al, 1986;Ramsay et al, 1986). Unlike the short halflife described in N-myc ampli®ed cell lines, the N-myc half-life in some cell lines is signi®cantly prolonged, resulting in an elevated steady-state protein level, perhaps due to an altered degradation signal (Cohn et al, 1990).…”

Analysis of EGF receptor amplicons reveals amplification of multiple expressed sequences

“…The expression of several oncogene products have been shown to be elevated in tumors for which the corresponding gene is ampli®ed, and these include c-erbB2/neu in breast cancer and ovarian cancer (Slamon et al, 1989), nmyc in neuroblastoma (Ramsay et al, 1986), and epidermal growth factor receptor in glioblastoma (Wong et al, 1987).…”

Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

“…The two translational forms of the Myc protein are expressed in all species of c-Myc examined so far (Hann and Eisenmann, 1984), as well as for N-Myc (Ramsay et al, 1986) and L-Myc proteins (DosakaAkita et al, 1991). The ratio of the two c-Myc proteins is disrupted in several tumor types, either due to rearrangement of the c-myc locus by chromosomal translocation, or speci®c point mutation resulting in the loss of c-Myc1 expression as in Burkitt's lymphoma cells or by increased c-Myc2 protein synthesis in other neoplastic cells (Hann and Eisenmann, 1984;Hann et al, 1988).…”