Downstream of human NDR kinases Impacting on c-myc and p21 protein stability to control cell cycle progression
Downstream of human NDR kinases Impacting on c-myc and p21 protein stability to control cell cycle progression
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DOI：
10.4161/cc.10.12.15826
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发表时间：
2011-06-15
期刊：
影响因子：
4.3
通讯作者：
Hemmings, Brian A.
中科院分区：
文献类型：
--
作者：
Cornils, Hauke;Kohler, Reto S.;Hemmings, Brian A.
哺乳动物基因组编码NDR/LATS激酶家族的4个成员：NDR1 （STK38）、NDR2 （STK38L）、LATS1和LATS2，从酵母到人类都高度保守。NDR/LATS激酶家族成员参与多种生物过程，从细胞分裂和形态到细胞凋亡和肿瘤抑制。在哺乳动物中，LATS1/2通过限制YAP/TAZ原癌基因的活性，作为HIPPO肿瘤抑制通路的中心部分。最近的证据表明NDR1/2也是延伸的HIPPO肿瘤抑制通路的一部分。除了在凋亡信号传导和肿瘤抑制方面的功能外，NDR1/2还参与控制HIPPO激酶同源物MST1和MST2下游的中心体复制和有丝分裂染色体排列。值得注意的是，我们最近也报道了NDR1/2控制着第三个MST家族成员MST3下游的G(1)/S转换。有趣的是，这个新描述的MST3-NDR1/2轴通过稳定c-myc和防止p21积累来促进G(1)进展，这表明NDR激酶具有潜在的促肿瘤作用。在这里，我们在更广泛的背景下讨论NDR激酶的这些新的细胞周期功能，并详细说明NDR激酶在正常和肿瘤生物学中的相反功能的可能解释。
The mammalian genome encodes 4 members of the NDR/LATS kinase family: NDR1 (STK38), NDR2 (STK38L), LATS1 and LATS2, which are highly conserved from yeast to man. Members of the NDR/LATS kinase family have been implicated in a variety of biological processes ranging from cell division and morphology to apoptosis and tumor suppression. In mammals LATS1/2 function as central parts of the HIPPO tumor suppressor pathway by restricting the activity of the YAP/TAZ proto-oncogenes. Recent evidence suggested that NDR1/2 are also part of an extended HIPPO tumor suppressor pathway. Apart from functions in apoptosis signaling and tumor suppression, NDR1/2 have been implicated in controlling centrosome duplication and mitotic chromosome alignment downstream of the HIPPO kinase homologs MST1 and MST2. Significantly, we also reported recently that NDR1/2 are controlling G(1)/S transition downstream of a third MST family member MST3. Intriguingly, this newly described MST3-NDR1/2 axis promotes G(1) progression by stabilizing c-myc and preventing p21 accumulation, indicating a potential pro-tumorigenic role for NDR kinases. Here we discuss these novel cell cycle functions of NDR kinases in a broader context and elaborate on possible explanations for the opposing functions of NDR kinases in normal and tumor biology.