PEA15 explained

Astrocytic phosphoprotein PEA-15 is a protein that in humans is encoded by the PEA15 gene.^{[1] [2]}

PEA15 is a death effector domain (DED)-containing protein predominantly expressed in the central nervous system, particularly in astrocytes.^[2]

PEA-15 promotes autophagy in glioma cells in a JNK-dependent manner.^[3]

Interactions

PEA15 has been shown to interact with:

• Caspase 8,^{[4] [5]}
• FADD,^{[4] [5]} and
• MAPK1,^[6]
• Phospholipase D1,^[7] and
• RPS6KA3.^[8]

Further reading

• Araujo H, Danziger N, Cordier J, Glowinski J, Chneiweiss H . Characterization of PEA-15, a major substrate for protein kinase C in astrocytes . J. Biol. Chem. . 268 . 8 . 5911–20 . 1993 . 10.1016/S0021-9258(18)53407-4 . 8449955 . free .
• Estellés A, Yokoyama M, Nothias F, Vincent JD, Glowinski J, Vernier P, Chneiweiss H . The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs conserved on their full length in mouse and human . J. Biol. Chem. . 271 . 25 . 14800–6 . 1996 . 8662970 . 10.1074/jbc.271.25.14800 . free .
• Condorelli G, Vigliotta G, Iavarone C, Caruso M, Tocchetti CG, Andreozzi F, Cafieri A, Tecce MF, Formisano P, Beguinot L, Beguinot F . PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus . EMBO J. . 17 . 14 . 3858–66 . 1998 . 9670003 . 1170721 . 10.1093/emboj/17.14.3858 .
• Kubes M, Cordier J, Glowinski J, Girault JA, Chneiweiss H . Endothelin induces a calcium-dependent phosphorylation of PEA-15 in intact astrocytes: identification of Ser104 and Ser116 phosphorylated, respectively, by protein kinase C and calcium/calmodulin kinase II in vitro . J. Neurochem. . 71 . 3 . 1307–14 . 1998 . 9721757 . 10.1046/j.1471-4159.1998.71031307.x . free .
• Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalò P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F . PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis . Oncogene . 18 . 31 . 4409–15 . 1999 . 10442631 . 10.1038/sj.onc.1202831 . 20510429 .
• Kitsberg D, Formstecher E, Fauquet M, Kubes M, Cordier J, Canton B, Pan G, Rolli M, Glowinski J, Chneiweiss H . Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis . J. Neurosci. . 19 . 19 . 8244–51 . 1999 . 10493725 . 10.1523/JNEUROSCI.19-19-08244.1999 . 6783010.
• Wolford JK, Bogardus C, Ossowski V, Prochazka M . Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians . Gene . 241 . 1 . 143–8 . 2000 . 10607908 . 10.1016/S0378-1119(99)00455-2 .
• Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA . Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them . J. Biol. Chem. . 275 . 45 . 35224–32 . 2001 . 10926929 . 10.1074/jbc.M003329200 . free.
• Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B, Nguyen XT, Barnier JV, Camonis J, Ginsberg MH, Chneiweiss H . PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase . Dev. Cell . 1 . 2 . 239–50 . 2001 . 11702783 . 10.1016/S1534-5807(01)00035-1 . free .
• Condorelli G, Trencia A, Vigliotta G, Perfetti A, Goglia U, Cassese A, Musti AM, Miele C, Santopietro S, Formisano P, Beguinot F . Multiple members of the mitogen-activated protein kinase family are necessary for PED/PEA-15 anti-apoptotic function . J. Biol. Chem. . 277 . 13 . 11013–8 . 2002 . 11790785 . 10.1074/jbc.M110934200 . free .
• Xiao C, Yang BF, Asadi N, Beguinot F, Hao C . Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells . J. Biol. Chem. . 277 . 28 . 25020–5 . 2002 . 11976344 . 10.1074/jbc.M202946200 . free .
• Vaidyanathan H, Ramos JW . RSK2 activity is regulated by its interaction with PEA-15 . J. Biol. Chem. . 278 . 34 . 32367–72 . 2003 . 12796492 . 10.1074/jbc.M303988200 . free .
• Trencia A, Perfetti A, Cassese A, Vigliotta G, Miele C, Oriente F, Santopietro S, Giacco F, Condorelli G, Formisano P, Beguinot F . Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action . Mol. Cell. Biol. . 23 . 13 . 4511–21 . 2003 . 12808093 . 164852 . 10.1128/MCB.23.13.4511-4521.2003 .
• Trencia A, Fiory F, Maitan MA, Vito P, Barbagallo AP, Perfetti A, Miele C, Ungaro P, Oriente F, Cilenti L, Zervos AS, Formisano P, Beguinot F . Omi/HtrA2 promotes cell death by binding and degrading the anti-apoptotic protein ped/pea-15 . J. Biol. Chem. . 279 . 45 . 46566–72 . 2004 . 15328349 . 10.1074/jbc.M406317200 . free .
• Gaumont-Leclerc MF, Mukhopadhyay UK, Goumard S, Ferbeyre G . PEA-15 is inhibited by adenovirus E1A and plays a role in ERK nuclear export and Ras-induced senescence . J. Biol. Chem. . 279 . 45 . 46802–9 . 2004 . 15331596 . 10.1074/jbc.M403893200 . free .
• Renganathan H, Vaidyanathan H, Knapinska A, Ramos JW . Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD . Biochem. J. . 390 . Pt 3 . 729–35 . 2006 . 15916534 . 1199667 . 10.1042/BJ20050378 .

Notes and References

1. Hwang S, Kuo WL, Cochran JF, Guzman RC, Tsukamoto T, Bandyopadhyay G, Myambo K, Collins CC . Assignment of HMAT1, the human homolog of the murine mammary transforming gene (MAT1) associated with tumorigenesis, to 1q21.1, a region frequently gained in human breast cancers . Genomics . 42 . 3 . 540–2 . September 1997 . 9205133 . 10.1006/geno.1997.4768 .
2. Web site: Entrez Gene: PEA15 phosphoprotein enriched in astrocytes 15.
3. Böck BC, Tagscherer KE, Fassl A, Krämer A, Oehme I, Zentgraf HW, Keith M, Roth W . The PEA-15 protein regulates autophagy via activation of JNK . J. Biol. Chem. . 285 . 28 . 21644–54 . July 2010 . 20452983 . 2898427 . 10.1074/jbc.M109.096628 . free .
4. Kitsberg D, Formstecher E, Fauquet M, Kubes M, Cordier J, Canton B, Pan G, Rolli M, Glowinski J, Chneiweiss H . Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis . J. Neurosci. . 19 . 19 . 8244–51 . October 1999 . 10493725 . 10.1523/JNEUROSCI.19-19-08244.1999 . 6783010.
5. Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalò P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F . PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis . Oncogene . 18 . 31 . 4409–15 . August 1999 . 10442631 . 10.1038/sj.onc.1202831 . 20510429 .
6. Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B, Nguyen XT, Barnier JV, Camonis J, Ginsberg MH, Chneiweiss H . PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase . Dev. Cell . 1 . 2 . 239–50 . August 2001 . 11702783 . 10.1016/s1534-5807(01)00035-1. free .
7. Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA . Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them . J. Biol. Chem. . 275 . 45 . 35224–32 . November 2000 . 10926929 . 10.1074/jbc.M003329200 . free.
8. Vaidyanathan H, Ramos JW . RSK2 activity is regulated by its interaction with PEA-15 . J. Biol. Chem. . 278 . 34 . 32367–72 . August 2003 . 12796492 . 10.1074/jbc.M303988200 . free .