Abstract
MYCN is a member of the MYC family of proto-oncogenes. It encodes a transcription factor, MYCN, involved in the control of fundamental processes during embryonal development. The MYCN protein is situated downstream of several signaling pathways promoting cell growth, proliferation and metabolism of progenitor cells in different developing organs and tissues. Conversely, deregulated MYCN signaling supports the development of several different tumors, mainly with a childhood onset, including neuroblastoma, medulloblastoma, rhabdomyosarcoma and Wilms’ tumor, but it is also associated with some cancers occurring during adulthood such as prostate and lung cancer. In neuroblastoma, MYCN-amplification is the most consistent genetic aberration associated with poor prognosis and treatment failure. Targeting MYCN has been proposed as a therapeutic strategy for the treatment of these tumors and great efforts have allowed the development of direct and indirect MYCN inhibitors with potential clinical use.
Highlights
IntroductionThe MYC proto-oncogene family includes three paralogs: c-MYC, MYCN and MYCL [1,2]
The MYC proto-oncogene family includes three paralogs: c-MYC, MYCN and MYCL [1,2].They are situated on different chromosomes (Table 1) and are expressed at specific times during development, but encode proteins with similar functional domains, including the trans-activating and DNA binding domains (Figure 1) [1]
MYCN is important in cell cycle progression and apoptosis and it is the dysfunction of these processes due to amplification of the MYCN gene that contributes to aggressive medulloblastoma [151,153]
Summary
The MYC proto-oncogene family includes three paralogs: c-MYC, MYCN and MYCL [1,2] They are situated on different chromosomes (Table 1) and are expressed at specific times during development, but encode proteins with similar functional domains, including the trans-activating and DNA binding domains (Figure 1) [1]. These proteins, c-MYC, MYCN and MYCL (here together referred to as “MYC”), are transcription factors that belong to a larger class of proteins which contain a basic-region/helix-loop-helix/leucine-zipper (bHLHZip) important for protein dimerization and sequence-specific DNA binding [3]. Aberrant MYC regulation can lead to increased cell proliferation and is commonly observed in cancers [2]
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