AMY‐1, a novel C‐MYC binding protein that stimulates transcription activity of C‐MYC

Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein

“…Among the 19 genes that contain at least one predicted binding site in their 3 0 -UTR for miR-22, each of the genes LRRC1, DPM2, NPNT, HNRNPA3 and MYCBP contains at least one putative target site that is conserved across mammalian species (Supplementary Table 2b). As miR-22 has a tumor-suppressive activity on tumor cell lines, and among these genes, only MYCBP was previously reported to have functions related to tumorigenesis (Taira et al, 1998;Sakamuro and Prendergast, 1999), we chose MYCBP to verify whether it is a target of miR-22 for mediating the inhibition of proliferation and growth of tumor cell lines. MYCBP is known to contribute to E-box-dependent transcriptional activation of a panel of genes by oncogenic transcription factor cMyc (Sakamuro and Prendergast, 1999), and thus might link miR-22 to its anti-growth action.…”

“…Previous studies have shown that MYCBP is engaged in the activation of E-box-dependent transcription by c-Myc to promote tumor cell growth (Taira et al, 1998;Sakamuro and Prendergast, 1999). Our study pinpointed MYCBP as a direct target of miR-22, thus To test this assertion, we selected several well identified E-box-dependent target genes, which include cyclin D2, cyclin-dependent kinase 4, ornithine decarboxylase, lactate dehydrogenase-A, carbamoyl phosphate synthase-aspartate transcarbamylasedihydroorotase, nucleolin and eukaryotic translation initiation factor 2A.…”

“…The control of c-Myc expression and function involves several mechanisms, one of which is based on the regulatory network of the c-Myc-binding proteins. The MYCBP (AMY-1) gene encodes a small c-Mycbinding protein of B11 kD, that binds the N-terminal domain of c-Myc through its C-terminal region and stimulates E-box-dependent transcriptional activation of c-Myc to promote tumorigenesis (Taira et al, 1998;Sakamuro and Prendergast, 1999). Several miRNAs have been found to regulate cell proliferation and anchorage-dependent growth (Esquela-Kerscher and Slack, 2006), but cross-talk between miRNAs and Myc genes has only started to emerge (Chang et al, 2008;Mestdagh et al, 2009).…”

Mechanisms of apoptosis by c-Myc

“…The activation activity of the NTD may also be influenced by interactions with the retinoblastoma (Rb)-related protein p107 (Beijersbergen et al, 1994;Gu et al, 1994;Hoang et al, 1995), whose binding to c-Myc may be modulated by cyclin D/CDK4 phosphorylation (Hass et al, 1997), or with the adaptor protein and tumor suppressor Bin1 (Sakamuro et al, 1996;Elliott et al, 1999). The NTD is also reported to interact with a-tubulin (Alexandrova et al, 1995), PAM, a large protein which includes RCC1-like repeats suggesting a role in chromatin regulation , MM-1, a nucleocytoplasmic adaptor protein that inhibits transactivation by c-Myc, and AMY-1, a small protein reported to potentiate the transactivation activity of cMyc (Taira et al, 1998). In addition to harboring a transactivation domain, the NTD also mediates transcriptional repression (Kaddurah-Daouk et al, 1987;Suen and Hung, 1991;Yang et al, 1991Yang et al, , 1993Jansen-Durr et al, 1993;Roy et al, 1993;Li et al, 1994;Philipp et al, 1994;Lee et al, 1996;Tikhonenko et al, 1997).…”

MSSP promotes ras/myc cooperative cell transforming activity by binding to c‐Myc

“…Two days after transfection, whole cell extracts were prepared by addition of the Triton X-100-containing solution from a Pica gene kit (Wako Pure Chemicals Co. Ltd, Kyoto) to the cells. About one-®fth of the volume of the extract was used for the bgalactosidase assay to normalize the transfection ef®ciency, as described previously (Mori et al 1998;Taira et al 1998) and the luciferase activity due to the reporter plasmid was determined using the Pica gene kit and a luminometer, Luminocounter ATP300 (Advantec Toyo Co. Ltd, Tokyo). The same experiments were repeated ®ve to 10 times.…”