Updates on HIPK2: a resourceful oncosuppressor for clearing cancer.
Updates on HIPK2: a resourceful oncosuppressor for clearing cancer.
复制标题
DOI：
10.1186/1756-9966-31-63
复制
发表时间：
2012-08-13
期刊：
影响因子：
--
通讯作者：
Soddu S
中科院分区：
文献类型：
--
作者：
D'Orazi G;Rinaldo C;Soddu S
同源结构域相互作用蛋白激酶2（HIPK 2）是一种多才多艺的蛋白质，它利用其激酶活性来调节癌症中的关键分子途径，以抑制肿瘤生长并诱导对治疗的反应。HIPK 2磷酸化抑癌基因p53以激活凋亡。此外，p53非依赖性凋亡途径也受HIPK 2调节，并且也可用于抗癌目的。因此，HIPK 2活性被认为是基因毒性损伤后靶向肿瘤细胞凋亡的中心开关，HIPK 2功能的保留和/或恢复对于肿瘤对治疗的有效反应至关重要。作为原理的证据，HIPK 2敲低损害p53功能，诱导体内化学抗性、血管生成和肿瘤生长，相反，HIPK 2过表达激活凋亡途径，抵消缺氧，抑制血管生成，并以p53依赖性和非依赖性方式诱导化学敏感性。HIPK 2基因敲除小鼠的研究也证实了HIPK 2在抑制肿瘤发展中的作用。最近的研究表明，HIPK 2抑制确实存在于肿瘤中，并依赖于几种机制，包括HIPK 2细胞质定位，蛋白质降解和杂合性丢失（洛），概括了通过RNA干扰研究在肿瘤细胞中获得的生物学结果，如p53失活，对治疗的抗性，凋亡抑制和肿瘤进展。这些发现可能会为治疗癌症患者带来新的诊断和治疗方法。本文就HIPK 2在肿瘤发生和肿瘤治疗中的作用作一综述。
Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented protein that exploits its kinase activity to modulate key molecular pathways in cancer to restrain tumor growth and induce response to therapies. HIPK2 phosphorylates oncosuppressor p53 for apoptotic activation. In addition, also p53-independent apoptotic pathways are regulated by HIPK2 and can be exploited for anticancer purpose too. Therefore, HIPK2 activity is considered a central switch in targeting tumor cells toward apoptosis upon genotoxic damage and the preservation and/or restoration of HIPK2 function is crucial for an efficient tumor response to therapies. As a proof of principle, HIPK2 knockdown impairs p53 function, induces chemoresistance, angiogenesis, and tumor growth in vivo, on the contrary, HIPK2 overexpression activates apoptotic pathways, counteracts hypoxia, inhibits angiogenesis, and induces chemosensitivity both in p53-dependent and -independent ways. The role of HIPK2 in restraining tumor development was also confirmed by studies with HIPK2 knockout mice. Recent findings demonstrated that HIPK2 inhibitions do exist in tumors and depend by several mechanisms including HIPK2 cytoplasmic localization, protein degradation, and loss of heterozygosity (LOH), recapitulating the biological outcome obtained by RNA interference studies in tumor cells, such as p53 inactivation, resistance to therapies, apoptosis inhibition, and tumor progression. These findings may lead to new diagnostic and therapeutic approaches for treating cancer patients. This review will focus on the last updates about HIPK2 contribution in tumorigenesis and cancer treatment.
登录
查看更多内容
影响因子：
8
作者：
Mao, J-H;Wu, D.;Kim, I-J;Kang, H. C.;Wei, G.;Climent, J.;Kumar, A.;Pelorosso, F. G.;DelRosario, R.;Huang, E. J.;Balmain, A.
通讯作者：
Balmain, A.
影响因子：
8
作者：
Di Stefano, V;Blandino, G;D'Orazi, G
通讯作者：
D'Orazi, G
影响因子：
8
作者：
Lazzari, C.;Prodosmo, A.;Soddu, S.
通讯作者：
Soddu, S.
影响因子：
21.3
作者：
Calzado, Marco A.;de la Vega, Laureano;Schmitz, M. Lienhard
通讯作者：
Schmitz, M. Lienhard
影响因子：
8
作者：
Li, X-L;Arai, Y.;Kitabayashi, I.
通讯作者：
Kitabayashi, I.