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AMPK and Apoptosis

AMPK and Apoptosis. Emeline Van Goethem José Manuel López.

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AMPK and Apoptosis

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  1. AMPK and Apoptosis Emeline Van Goethem José Manuel López Apoptosis or programmed cell death is an important part of the development of all multicellular organisms and controls homeostasis and tissue modeling. In the cell there are mitochondrial dependent and independent pathways to induce apoptosis. Mitochondria Cytochrome c Caspase activation

  2. AMPK: Energy Homeostasis and Apoptosis AMPK is conserved between different species (Blast & ClustalW analysis)

  3. AIM Consensus sequence Looking for an Apoptotic protein Regulated by AMPK (X,)XXS/TXXX FEBS Letters 361 (1995) 191-195 Dale S., et al. : MVLIF : R>K>H Expasy Tools Scan Prosite [MVLIF]x(0,1)[RKH]xx[ST]xxx[MVLIF] Target proteins for AMPK Homo sapiens >1000 Xenopus laevis 678 Xenopus laevis + mitochondria 17 VDAC2 (Voltage dependent anion channel 2) Regulates cytochrome c release / apoptosis

  4. Xenopus VDAC isoforms (Blast Search) VDAC2 -AVPPSYADLGKSARDIFNKGYGFGLVKLDVKTKSATGVEFTTSGTSNTDSGKVNGSLET VDAC1 MAIPPAYVDLGKSARDIFTKGYGFGFIKLDLKTKSENGLEFTSSGSANAETSKVSGNLET MGC81430 MAVPPTYADLGKSARDVFNKGYGFGLVKLEVKTKSSSGVEFTSSGSSNTDTGKASGNLET VDAC2 KYKWGEYGLTFTEKWNTDNTLGTEIAIEDQIAKGLKLTFDTTFSPNTGKKSGKVKAAYKQ VDAC1 KYKWAEYGLTFTEKWNTDNTLGTEITVEDQLAKGLKLTFDSSFSPNTGKKNAKVKSAYKR MGC81430 KYKMKETGLTFTQKWNTDNTLGTEVALEDKLAKGLKLSLDTTFVPNTGKKSAKLKTSYKR VDAC2 EYVNLGCDVDFDFAGPAIHGSAVVGYEGWLAGYQMTFDSAKSKLTKNNFAVGYKTGDFQL VDAC1 EHLNVGCDMDFDIAGPSVRGAVVFGYEGWLAGYQMTFESSKSRVSQSNFAVGYKTDEFQL MGC81430 DYANLGIDIDLDLAGPTIYGWGVLGYQGWLAGYQMAFDTAKSRLAQNNFALGYTAGDFQL VDAC2 HTNVNDGSEFAGSIYQKVSDKMETAVNLAWTSGNNSTRFGIAAKYQLDSHAAISAKVNNS VDAC1 HTNVNDGTDFGGSVYQKVNDKLETAINLAWTAGNSNTRFGIAAKYQIDSDASFSAKVNNS MGC81430 HTNVNDGTEFGGSVYQKVSKDVETSVSLAWSAGSNNTRFGIGAKYQLDSNTTISAKVNNA VDAC2 SLVGVGYTQTLRPGVKLTLSALVDGKNINAGGHKLGLGLELEA VDAC1 SLIGLGYTQTLKPGIKLTLSTLVDGKNINAGGHKLGLGLEFEA MGC81430 SLIGVGYTQTLRPGVKLTLSALVNGKNFSAGGHKVGLGFELEA AMPK consensus sequence is preserved in Xenopus VDAC 1,2,3 isoforms

  5. Checking for a transmembrane domain in VDAC2 Kdoolite hydrophobicity result Query Statistics: Window Size = 19 Start Position = 1 End Position = 282 Query Length = 282 Effective Length = 264 When the window size is 19, peaks with scores greater than 1.8 (red line ) indicate possible transmembrane regions. The score at window position 1 is the average hydropathy of the 19 amino acids from position 1 to position 19 in the input sequence.

  6. Other Protein Kinases can phosphorylate VDAC2? Scan Site Motif Scan PKC

  7. Conclusions AMPK is conserved in different species VDAC isoforms (1,2,3) are present in Xenopus VDAC could be a target of Xenopus AMPK Open Questions... Why VDAC does not show hydrophobic domain with Kdoolite program? How accesible is the AMPK phosphorylation site in VDAC?

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