The UHRF family: oncogenes that are drugable targets for cancer therapy in the near future?
In this paper, we review the current literature about the UHRF family that in particular includes the UHRF1 and UHRF2 genes. Its members play a fundamental role in cell proliferation through different structural domains. These domains include a ubiquitin-like domain (NIRF_N), a plant homeodomain (PHD) domain, a SRA domain and a RING domain. The SRA domain has only been observed in this family probably conferring unique properties to it. The unique enzymatic activity so far identified in this family involves the RING finger that contains a ubiquitin E3 ligase activity toward, for instance, histones. The physiological roles played by the UHRF family are most likely exerted during embryogenic development and when proliferation is required in adults. Interestingly, UHRF members are putative oncogenes regulated by tumor suppressor genes, but they exert also a feedback control on these latter. Finally, we propose some new roles for this family, including regulation and/or inheritance of the epigenetic code. Alteration of these regulatory mechanisms, such as those occurring in cancer cells, may be involved in carcinogenesis. The reasons why the UHRF family could be an interesting target for developing anticancer drugs is also developed.
CNRS UMR 7175, Département de Pharmacologie et Pharmacochimie des Interactions Moléculaires et Cellulaires, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401, Illkirch Cedex, France. christian.bronner@pharma.u-strasbg.fr
Christian
C
Bronner
Mayada
M
Achour
Yoshimi
Y
Arima
Thierry
T
Chataigneau
Hideyuki
H
Saya
Valérie B
VB
Schini-Kerth
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D009857:Oncogenes / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D022762:CCAAT-Enhancer-Binding Proteins; D009687:Nuclear Proteins; C406364:UHRF1 protein, human; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases; C117054:Uhrf1 protein, mouse