Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity.
Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity.
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DOI：
10.1371/journal.pone.0036909
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Romeo G
中科院分区：
文献类型：
--
作者：
Chiantore MV;Vannucchi S;Accardi R;Tommasino M;Percario ZA;Vaccari G;Affabris E;Fiorucci G;Romeo G
干扰素(IFN)-β抑制粘膜高危人乳头瘤病毒（HPV）和皮肤HPV E6和E7蛋白转化的角质形成细胞的细胞增殖并影响细胞周期。特别是，在较长时间的IFN-β治疗后，皮肤表达HPV38的细胞会发生衰老。IFN-β似乎通过上调肿瘤抑制因子PML（一种众所周知的IFN诱导基因）的表达来诱导衰老。事实上，通过特定sirna进行的基因沉默实验表明，PML在衰老程序的执行中是必不可少的，p53和p21途径都参与其中。IFN-β治疗导致p53磷酸化和乙酰化状态的调节以及p53显性阴性ΔNp73表达的减少。这些作用允许p53反激活活性参与控制细胞增殖的靶基因的恢复。综上所述，这些研究表明通过IFN通路的信号传导可能在细胞衰老中起重要作用。对IFN抗肿瘤作用和影响肿瘤反应性或耐药机制的进一步了解有助于进一步开发IFN治疗癌症的生物分子策略。
Interferon (IFN)-β inhibits cell proliferation and affects cell cycle in keratinocytes transformed by both mucosal high risk Human Papilloma Virus (HPV) and cutaneous HPV E6 and E7 proteins. In particular, upon longer IFN-β treatments, cutaneous HPV38 expressing cells undergo senescence. IFN-β appears to induce senescence by upregulating the expression of the tumor suppressor PML, a well known IFN-induced gene. Indeed, experiments in gene silencing via specific siRNAs have shown that PML is essential in the execution of the senescence programme and that both p53 and p21 pathways are involved. IFN-β treatment leads to a modulation of p53 phosphorylation and acetylation status and a reduction in the expression of the p53 dominant negative ΔNp73. These effects allow the recovery of p53 transactivating activity of target genes involved in the control of cell proliferation. Taken together, these studies suggest that signaling through the IFN pathway might play an important role in cellular senescence. This additional understanding of IFN antitumor action and mechanisms influencing tumor responsiveness or resistance appears useful in aiding further promising development of biomolecular strategies in the IFN therapy of cancer.
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影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
13.6
作者：
Dai C;Gu W
通讯作者：
Gu W
影响因子：
4.8
作者：
Gabet, Anne-Sophie;Accardi, Rosita;Tommasino, Massimo
通讯作者：
Tommasino, Massimo
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.4
作者：
Caldeira, S;Zehbe, I;Tommasino, M
通讯作者：
Tommasino, M