Control of tumorigenesis and chemoresistance by the DEK oncogene.
Slight modifications of chromatin dynamics can translate into small- and large-scale changes in DNA replication and DNA repair. Similarly, promoter usage and accessibility are tightly dependent on chromatin architecture. Consequently, it is perhaps not surprising that factors controlling chromatin organization are frequently deregulated (directly or indirectly) in cancer cells. DEK is emerging as a novel class of DNA topology modulators that can be both targets and effectors of protumorigenic events. The locus containing DEK at chromosome 6p22.3 is amplified or reorganized in multiple cancer types. In addition, DEK can be subject to a variety of tumor-associated transcriptional and post-translational modifications. In turn, DEK can favor cell transformation, at least in part by inhibiting cell differentiation and premature senescence. More recently, DEK has also been linked to the resistance of malignant cells to apoptotic inducers. Interestingly, a fraction of DEK can also bind RNA and affect alternative splicing, further illustrating the pleiotropic roles that this protein may exert in cancer cells. Here we will summarize the current literature about the regulation and function(s) of DEK as a proto-oncogene. In addition, the translational relevance of DEK as a putative diagnostic marker and candidate for drug development will be discussed.
Riveiro-Falkenbach
Erica
E
Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre), Madrid, Spain.
Soengas
María S
MS
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011499:Protein Processing, Post-Translational; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas