CREB Phosphorylation Promotes Nerve Cell Survival
The cyclic AMP-responsive element binding protein (CREB) is a posttranslationally activated transcription factor that has been implicated in numerous brain functions including cell survival. In this study we investigated whether CREB overexpression using transient transfection of a pAAV/CMV-CREB pla...
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| Veröffentlicht in: | Journal of neurochemistry 1999-11, Vol.73 (5), p.1836-1842 |
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| container_end_page | 1842 |
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| container_issue | 5 |
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| container_title | Journal of neurochemistry |
| container_volume | 73 |
| creator | WALTON, M WOODGATE, A.-M MURAVLEV, A RUIAN XU DURING, M. J DRAGUNOW, M |
| description | The cyclic AMP-responsive element binding protein (CREB) is a posttranslationally activated transcription factor that has been implicated in numerous brain functions including cell survival. In this study we investigated whether CREB overexpression using transient transfection of a pAAV/CMV-CREB plasmid altered neuronal cells' susceptibility to apoptosis. We found that elevated CREB protein inhibited apoptosis induced by okadaic acid. At least part of this effect is critically dependent on prolonged Ser133 phosphorylation, as a directed mutation at this site decreased CREB-induced protection. These results suggest that CREB is a survival factor for neuronal cells and that treatments aimed at augmenting CREB phosphorylation in the brain may be neuroprotective. |
| doi_str_mv | 10.1046/j.1471-4159.1999.01836.x |
| format | Article |
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J</creatorcontrib><creatorcontrib>DRAGUNOW, M</creatorcontrib><title>CREB Phosphorylation Promotes Nerve Cell Survival</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>The cyclic AMP-responsive element binding protein (CREB) is a posttranslationally activated transcription factor that has been implicated in numerous brain functions including cell survival. In this study we investigated whether CREB overexpression using transient transfection of a pAAV/CMV-CREB plasmid altered neuronal cells' susceptibility to apoptosis. We found that elevated CREB protein inhibited apoptosis induced by okadaic acid. At least part of this effect is critically dependent on prolonged Ser133 phosphorylation, as a directed mutation at this site decreased CREB-induced protection. These results suggest that CREB is a survival factor for neuronal cells and that treatments aimed at augmenting CREB phosphorylation in the brain may be neuroprotective.</description><subject>Ageing, cell death</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell physiology</subject><subject>Cell Survival</subject><subject>Cyclic AMP Response Element-Binding Protein - genetics</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Neurons - physiology</subject><subject>okadaic acid</subject><subject>Okadaic Acid - pharmacology</subject><subject>PC12 Cells</subject><subject>Phosphorylation</subject><subject>Phosphoserine - metabolism</subject><subject>Rats</subject><subject>Transfection</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1PwkAQhjdGI4j-BdOD8dY6w2734-BBG_wKQeLHebMt21BSKO5ShH9vK0Q9eppJ5pmZNw8hAUKEwPjVLEImMGQYqwiVUhGgpDzaHJDuz-CQdAH6_ZAC63fIifczAOSM4zHpIMRUAMMuweRlcBuMp5VfTiu3Lc2qqBbB2FXzamV9MLJubYPElmXwWrt1sTblKTnKTent2b72yPvd4C15CIfP94_JzTDMYoY8TM1EWMUZZUwiKEhBcZFJi_FExiyXTUw7MdRIkfapjKVKMQVh8ywXSjHBaY9c7u4uXfVRW7_S88JnTRKzsFXtNQqquFKyAeUOzFzlvbO5XrpibtxWI-hWl57p1opurehWl_7WpTfN6vn-R53O7eTP4s5PA1zsAeMzU-bOLLLC_3KoJEhosOsd9lmUdvvv__pplLQd_QKYPYOA</recordid><startdate>199911</startdate><enddate>199911</enddate><creator>WALTON, M</creator><creator>WOODGATE, A.-M</creator><creator>MURAVLEV, A</creator><creator>RUIAN XU</creator><creator>DURING, M. 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Psychology</topic><topic>Gene Expression</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Neurons - physiology</topic><topic>okadaic acid</topic><topic>Okadaic Acid - pharmacology</topic><topic>PC12 Cells</topic><topic>Phosphorylation</topic><topic>Phosphoserine - metabolism</topic><topic>Rats</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WALTON, M</creatorcontrib><creatorcontrib>WOODGATE, A.-M</creatorcontrib><creatorcontrib>MURAVLEV, A</creatorcontrib><creatorcontrib>RUIAN XU</creatorcontrib><creatorcontrib>DURING, M. 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| subjects | Ageing, cell death Animals Apoptosis - drug effects Biological and medical sciences Cell physiology Cell Survival Cyclic AMP Response Element-Binding Protein - genetics Cyclic AMP Response Element-Binding Protein - metabolism Fundamental and applied biological sciences. Psychology Gene Expression L-Lactate Dehydrogenase - metabolism Molecular and cellular biology Neurons - physiology okadaic acid Okadaic Acid - pharmacology PC12 Cells Phosphorylation Phosphoserine - metabolism Rats Transfection |
| title | CREB Phosphorylation Promotes Nerve Cell Survival |
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