%0 Journal Article
%T Regulation of MCP-1 chemokine transcription by p53
%A Katrin Hacke
%A Bladimiro Rincon-Orozco
%A Gilles Buchwalter
%A Simone Y Siehler
%A Bohdan Wasylyk
%A Lisa Wiesm¨¹ller
%A Frank R£¿sl
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-82
%X The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-¦Á can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-¦Á treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-¦Á addition, directly confirming a crosstalk between p53 and MCP-1.These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment.Chemokines play a crucial role in innate and adaptive immunity by attracting and activating specific subsets of effector leukocytes, cells from the monocyte/macrophage lineage as well as natural killer cells. Accordingly, these kinds of exoproteins are involved in many physiological processes such as cell proliferation, apoptosis, tumor metastasis and host defense [1]. The monocyte-chemoattractant protein-1 (MCP-1), a well-known member of the CC subgroup chemokine family, has been linked with chronic inflammatory diseases [2,3] antitumor immunity [4,5], atherosclerosis [6] and cervical cancer [7-9].Like many other human malignancies, development of cervical cancer is a multi-step process, which is initiated by the infection of "high-risk" types of human papilloma viruses (HPV) such as HPV 16 or HPV 18. The transforming potential is encoded by the open reading frames E6 and E7. Both oncoproteins exert pleiotropic functions
%U http://www.molecular-cancer.com/content/9/1/82