We reported previously that protein kinase C␣ (PKC␣), a negative regulator of cell growth in the intestinal epithelium, inhibits cyclin D1 translation by inducing hypophosphorylation/activation of the translational repressor 4E-BP1. The current study explores the molecular mechanisms underlying PKC/PKC␣-induced activation of 4E-BP1 in IEC-18 nontransformed rat ileal crypt cells. PKC signaling is shown to promote dephosphorylation of Thr 45 and Ser 64 on 4E-BP1, residues directly involved in its association with eIF4E. Consistent with the known role of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway in regulation of 4E-BP1, PKC signaling transiently inhibited PI3K activity and Akt phosphorylation in IEC-18 cells. However, PKC/PKC␣-induced activation of 4E-BP1 was not prevented by constitutively active mutants of PI3K or Akt, indicating that blockade of PI3K/Akt signaling is not the primary effector of 4E-BP1 activation. This idea is supported by the fact that PKC activation did not alter S6 kinase activity in these cells. Further analysis indicated that PKC-mediated 4E-BP1 hypophosphorylation is dependent on the activity of protein phosphatase 2A (PP2A). PKC signaling induced an ϳ2-fold increase in PP2A activity, and phosphatase inhibition blocked the effects of PKC agonists on 4E-BP1 phosphorylation and cyclin D1 expression. H 2 O 2 and ceramide, two naturally occurring PKC␣ agonists that promote growth arrest in intestinal cells, activate 4E-BP1 in PKC/PKC␣-dependent manner, supporting the physiological significance of the findings. Together, our studies indicate that activation of PP2A is an important mechanism underlying PKC/ PKC␣-induced inhibition of cap-dependent translation and growth suppression in intestinal epithelial cells. Members of the protein kinase C (PKC)3 family of signal transduction molecules have been implicated in regulation of fundamental cellular processes, including cell growth and cell cycle progression, differentiation, survival/apoptosis, protein translation, membrane trafficking, receptor desensitization, and migration (1-10). Increasing evidence supports a key role for PKC signaling in the maintenance of intestinal homeostasis (1,11,12), and aberrations in PKC expression and function occur early during intestinal tumorigenesis (13). Previous studies from this laboratory have demonstrated that PKC/PKC␣ signaling triggers a program of cell cycle withdrawal in intestinal epithelial cells characterized by rapid down-regulation of cyclin D1, increased expression of Cip/Kip cyclin-dependent kinase inhibitors, and activation of the growth suppressor function of members of the pocket protein family (14, 15). Downregulation of cyclin D1 precedes various hallmark events of cell cycle exit, pointing to the importance of regulation of this cyclin in PKC-mediated growth arrest in intestinal epithelial cells.Analysis of the mechanisms underlying PKC/PKC␣-mediated down-regulation of cyclin D1 identified PKC␣ as a negative regulator of cyclin D1 translation (7). PKC/PKC␣ signaling activates t...

A global collaborative effort is pivotal to conquer cancer. Themed 野Emerging role of China in global

In April 2013, the US Chinese Anti-Cancer Association (USCACA) held its 5th annual meeting in conjunction with the American Association for Cancer Research (AACR) 2013 Annual Meeting in Washington DC. The USCACA executive committee reported activities and programs and highlighted the partnership and collaboration between USCACA and other major organizations. The key initiatives and programs of USCACA included 1) USCACA-TIGM Esophageal Cancer Program that funds translational research of esophageal cancer prevention and treatment at the Xinxiang Medical University in Henan province, China; 2) the USCACA-NFCR-AFCR Scholarship Program, which has supported 10 young outstanding Chinese cancer researchers and will award 4 fellowships at the Guangzhou International Symposium on Oncology in November this year; 3) USCACA-Hengrui Training Program for Early Phase Clinical Research, which has supported the training of a Chinese scholar at two major cancer centers in the US; and 4) USCACA has continued its partnership with the Chinese Journal of Cancer, which has reached significant international impact

With the continuous development of technology, computer internet technology gradually began to spread, especially in the field of education. One important component of the structure at the moment the background information network, the network has become a modern teaching in the university indispensable. Through the internet, enables the traditional teaching model has been changed to improve the efficiency and quality of modern teaching in colleges. However, with respect to language, mathematics, and many other courses, the college public education system has been the subject of basketball have not have the appropriate network-based teaching system. In this paper, a brief analysis of the current situation in the network age college public basketball teaching system, and on this basis, the teaching system of Public Basketball Teaching Process under the Network Background Construction in depth, hoping for the college public basketball Teaching Efficiency of China and enhance the quality of teaching to bring some help.