Biology Department Faculty
Laura E. Hake
Associate Professor
Laura E. Hake
Ph.D.
Contact
Higgins Hall 444B
Telephone: 617-552-1935
Email: laura.hake@uc1112.com
Education
- Ph.D., Tufts University
Research Interests
减数分裂和动物早期发育过程中的翻译调控和信号转导.
Department
Research
Gene expression can be regulated at several different levels. 虽然基因表达的主要控制在转录水平(从DNA模板合成特定mrna)，但近年来，翻译水平(从信使RNA合成蛋白质)的调控也非常重要.
与mRNA poly(A)尾巴长度变化相关的翻译调控对于减数分裂的进展是必要的, early development and localized translation at the neuronal synapse. This mechanism is called “polyadenylation induced translation”. Essentially, mRNAs containing a long poly A tail (50-300 nt) are translated, whereas those with a short poly A tail (<50 nt) are not. 因此，改变poly - A尾部长度的分子事件可以直接影响mRNA的翻译.
C-mos mRNA在I前期卵母细胞中受CPEB相互作用的翻译抑制, a repressing protein complex and the cap binding protein eIF4E. During progesterone stimulated meiotic resumption, XGef influences the phosphorylation of CPEB by Aurora A kinase. This activates CPEB, which then recruits a complex of proteins, 裂解和聚腺苷化特异性因子和聚A聚合酶(CPSF和PAP), to the mRNA, and the poly A tail is elongated. 然后，多分子聚A结合蛋白(PABP)与聚A尾部结合，将eIF4G招募到mRNA中. This assists in displacement of the repressing complex, 43 S核糖体被招募到mRNA上启动翻译起始的扫描阶段.
我们目前的太阳城官网重点是剖析聚腺苷酸诱导翻译的分子机制和调控这一过程的信号转导级联 Xenopus oocyte meiosis.
Oocytes in most metazoans are frozen in prophase of meiosis I. Meiosis is reinitiated by the action of hormones on the oocyte membrane. In Xenopus oocytes, 类固醇激素触发一个信号转导级联，激活至少两个独立的途径，汇聚激活成熟促进因子(MPF)。, a powerful kinase that is the work horse of meiosis. In one pathway, Cdc25 phosphatase is activated, and it then removes an inhibitory phosphate from one of the subunits of MPF. In a parallel pathway (see figure below), 编码Mos激酶的mRNA的翻译被多聚腺苷酸诱导的翻译激活. 后一种途径对我们特别感兴趣，因为它将信号转导级联与特定的翻译调节机制联系起来.
由孕激素激活孕激素受体(PR)引起的信号转导级联, through the activation of Aurora A kinase, and the influence of Aurora A kinase and XGef on early CPEB activation. 然后CPEB参与多聚腺苷化诱导的c-mos mRNA翻译, which triggers the activation of mitogen activated protein kinase (MAPK). Activated MAPK, 结合多腺苷化诱导的细胞周期蛋白翻译和Cdc25的激活(未显示)刺激MPF(细胞周期蛋白B: cdc2)的及时激活。, which subsequently triggers resumption of meiosis. 箭头表示进一步刺激c-mos mRNA翻译的正反馈通路.
We use Xenopus 卵母细胞和卵子，因为我们可以获得大量的材料来太阳城官网聚腺苷酸诱导的翻译的分子机制，我们可以通过向外植的卵母细胞中添加黄体酮来诱导减数分裂信号转导级联. 显微注射使我们能够探索各种mrna和蛋白质对减数分裂和减数分裂成分代谢和聚腺苷化诱导翻译的影响.
Selected Publications
- Keady, B.T., Kuo, P., Martínez, S.E., Yuan, L., and Hake, L.E. 2007. MAPK与XGef相互作用，是细胞减数分裂过程中CPEB激活所必需的 Xenopus oocytes. Journal of Cell Science 120(6): 1093–1103.
- Martinez, S., Yuan, L., Lacza, C., Ransom, H., Mahon, G. M., Whitehead, I. P. and Hake, L. E. 2005. XGef mediates early phosphorylation of CPEB during Xenopus oocyte meiotic maturation. Molecular Biology of the Cell 16: 1152–64.
- Reverte, C. G., Yuan, L., Keady, B. T., Attfield, K. R., Mahon, G. M., Freeman, B., Whitehead, I. P., and Hake, L. E. 2003. XGef is a CPEB-interacting protein involved in Xenopus oocyte maturation. Developmental Biology 255: 383–398.
- Keady, B.T., Attfield, K. R., and Hake, L. E. 2002. Differential processing of the Xenopus ATP(CTP):tRNA nucleotidyltransferase mRNA. Biochemical and Biophysical Research Communications 297: 573–580.
- Reverte, C. G., Ahearn, M. D., and Hake, L. E. 2001. Stockpiling and degradation of CPEB during Xenopus oogenesis and oocyte maturation. Developmental Biology 231: 447–458.
- Mendez, R., Hake, L. E., Andresson, T., Littlepage, L. E. Ruderman, J. V., and Richter, J. D. 2000. Phosphorylation of CPEB by Eg2 regulates c-mos mRNA translation. Nature 404: 302–307.
- Chavous, D. A., Hake, L. E., Lynch, R. P. and O'Connor, C. M. 2000. 单倍体精子中异天冬氨酸甲基转移酶独特转录物的翻译:对蛋白质储存和修复的影响. Molecular Reproduction and Development 56: 1–6.
- Walker, J., Minshall, N., Hake, L. E., Richter, J., and Standart, N. 1999. 蛤3' UTR屏蔽元件结合蛋白p82是CPEB家族的成员. RNA 5: 14–26.
- Hake, L. E., Mendez, R., and Richter, J. D. 1998. CPEB结合RNA的特异性:对RRMs和一种新型锌指的要求. Molecular and Cellular Biology 18: 685–693.
- Hake, L. E., and Richter, J. D. 1997. Translational regulation of maternal mRNAs. BBA Reviews on Cancer 133: M31–M38.
- Stebbins-Boaz, B., Hake, L. E., and Richter, J. D. 1996. CPEB controls the cytoplasmic polyadenylation of cyclin, cdk2 and c-mos mRNAs and is necessary for oocyte maturation in Xenopus. EMBO Journal 15: 2582–2592.
- Hake, L. E., and Richter, J. D. 1994. CPEB是一种特异性因子，介导细胞胞质聚腺苷酸化 Xenopus oocyte maturation. Cell 79: 617–627.
- Hake, L. E., and Hecht, N. B. 1993. 利用小鼠体细胞色素c的另一个转录起始位点产生睾丸特异性1.7 kb cytochrome c mRNA. Journal of Biological Chemistry 268: 4788–4797.