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- 주제어 : nuclear Akt signaling (검색결과 2 건)
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Jeong, Sun Ah,Kim, Kuglae,Lee, Ji Hoon,Cha, Jeong Seok,Khadka, Prabhat,Cho, Hyun-Soo,Chung, In Kwon The Company of Biologists Ltd. 2015 Journal of cell science Vol.128 No.12
<P>Telomeres are essential for chromosome integrity and protection, and their maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have shown that human telomerase reverse transcriptase (hTERT) contains a bipartite nuclear localization signal (NLS; residues 222-240) that is responsible for nuclear import, and that Akt-mediated phosphorylation of residue S227 is important for efficient nuclear import of hTERT. Here, we show that hTERT binds to importin-alpha proteins through the bipartite NLS and that this heterodimer then forms a complex with importin-beta proteins to interact with the nuclear pore complex. Depletion of individual importin-alpha proteins results in a failure of hTERT nuclear import, and the resulting cytoplasmic hTERT is degraded by ubiquitin-dependent proteolysis. Crystallographic analysis reveals that the bipartite NLS interacts with both the major and minor sites of importin-alpha proteins. We also show that Akt-mediated phosphorylation of S227 increases the binding affinity for importin-alpha proteins and promotes nuclear import of hTERT, thereby resulting in increased telomerase activity. These data provide details of a binding mechanism that enables hTERT to interact with the nuclear import receptors and of the control of the dynamic nuclear transport of hTERT through phosphorylation.</P>
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Neuroprotection Signaling of Nuclear Akt in Neuronal Cells
안지인 한국뇌신경과학회 2014 Experimental Neurobiology Vol.23 No.3
Akt is one of the central kinases that perform a pivotal function in mediating survival signaling in a wide range of neuronal cell typesin response to growth factor stimulation. The recent findings of a number of targets for Akt suggest that it prohibits neuronal deathby both impinging on the cytoplasmic cell death machinery and by regulating nuclear proteins. The presence of active Akt in thenuclei of mammalian cells is no longer debatable, and this has been corroborated by the finding of multiple targets in the nucleus ofPC12 cells. However, it is also clear that the nuclear Akt signaling exists independent of the cytosolic Akt signaling, thereby showinga distinctive feature of nuclear Akt signaling as opposed to its cytosolic counterpart. The principal objective of this review is tosummarize our current state of knowledge regarding nuclear Akt signaling in neuronal survival, and to introduce current theoriesregarding the roles of nuclear Akt in neuron.
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