哇拉拉 这是我写得最长的一次了...
在教室写的感觉就是不一样呢
恩 以后都去教室写了
This week’s JC paper reports a novel discovery that the membrane associated form protein—Ku can interact with metalloproteinase 9 (MMP-9) at the cell surface, and this interaction may have important roles in tumor cell invasion and some other physiological processes.
Here again, the authors used the yeast two-hybrid system to screen the target protein by using Ku as the bait, and successfully identified MMP-9. I am deeply impressed by this powerful and useful tool as also shown in the past several JC papers.
However, the interaction of Ku and MMP-9 in yeast two-hybrid system is not strong enough to support the idea that they can actually interact with each other in mammalian cells or in vivo. The authors then investigated the interaction by using co-immunoprecipitation, determined the core regions required for this interaction in both MMP-9 and Ku, found that this interaction is exclusive or specific to Ku and MMP-2 didn’t interact with it. Finally, they demonstrated the Ku/ MMP-9 complex was present at the cell surface, furthermore, Ku and MMP-9 colocalized at the leading edge of the cells, and by using Ku directed antibodies they found the MMP-9 involved cellular invasion of collagen IV matrices was blocked, which implied a possible function of the Ku/ MMP-9 interaction.
In the discussion section, the authors hypothesized that the Ku was secreted to the membrane and associated to some unknown integral membrane proteins. Based on the fact the Ku is expressed in the nucleus in all primate cells but just express on membrane in some particular cells, such as tumors, it is quite possible that the existence of Ku in membrane must have some potentially important functions, as shown in some previously demonstrated cases that the membrane associated form Ku might have been involved in cell adhesive and proteolytic process. Now here, a new function may be added that the Ku may act as a docking molecular to assist MMP-9 in basement degradation pathway.
Interestingly, the Ku is formerly known because of its role in DNA double-strand breaks repair, while here it participated in the invasive pathway. The duel roles of Ku, prosurvival and proinvasive, can be explained by its different subcellular localizations, and these two totally opposite pathways must have their own molecular mechanism and signal network, which may then deserve further investigation.
Finally, the block of MMP-9 involved invasive pathway via Ku directed antibodies proposed another possible way for tumor therapy, as one of the most typical characteristics of tumor is its invasive ability, by blocking this pathway might provides an ideal way. However, there is still a long way to go, e.g, whether this method would work in vivo, or what other consequences would happen if blocking this process by using inhibitor of Ku.
在教室写的感觉就是不一样呢
恩 以后都去教室写了
This week’s JC paper reports a novel discovery that the membrane associated form protein—Ku can interact with metalloproteinase 9 (MMP-9) at the cell surface, and this interaction may have important roles in tumor cell invasion and some other physiological processes.
Here again, the authors used the yeast two-hybrid system to screen the target protein by using Ku as the bait, and successfully identified MMP-9. I am deeply impressed by this powerful and useful tool as also shown in the past several JC papers.
However, the interaction of Ku and MMP-9 in yeast two-hybrid system is not strong enough to support the idea that they can actually interact with each other in mammalian cells or in vivo. The authors then investigated the interaction by using co-immunoprecipitation, determined the core regions required for this interaction in both MMP-9 and Ku, found that this interaction is exclusive or specific to Ku and MMP-2 didn’t interact with it. Finally, they demonstrated the Ku/ MMP-9 complex was present at the cell surface, furthermore, Ku and MMP-9 colocalized at the leading edge of the cells, and by using Ku directed antibodies they found the MMP-9 involved cellular invasion of collagen IV matrices was blocked, which implied a possible function of the Ku/ MMP-9 interaction.
In the discussion section, the authors hypothesized that the Ku was secreted to the membrane and associated to some unknown integral membrane proteins. Based on the fact the Ku is expressed in the nucleus in all primate cells but just express on membrane in some particular cells, such as tumors, it is quite possible that the existence of Ku in membrane must have some potentially important functions, as shown in some previously demonstrated cases that the membrane associated form Ku might have been involved in cell adhesive and proteolytic process. Now here, a new function may be added that the Ku may act as a docking molecular to assist MMP-9 in basement degradation pathway.
Interestingly, the Ku is formerly known because of its role in DNA double-strand breaks repair, while here it participated in the invasive pathway. The duel roles of Ku, prosurvival and proinvasive, can be explained by its different subcellular localizations, and these two totally opposite pathways must have their own molecular mechanism and signal network, which may then deserve further investigation.
Finally, the block of MMP-9 involved invasive pathway via Ku directed antibodies proposed another possible way for tumor therapy, as one of the most typical characteristics of tumor is its invasive ability, by blocking this pathway might provides an ideal way. However, there is still a long way to go, e.g, whether this method would work in vivo, or what other consequences would happen if blocking this process by using inhibitor of Ku.
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