PDCD6 explained

Programmed cell death protein 6 is a protein that in humans is encoded by the PDCD6 gene.^[1]

This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant.^[2]

Interactions

PDCD6 has been shown to interact with ASK1,^[3] PDCD6IP,^{[4] [5]} Fas receptor,^[6] ANXA11^[5] and PEF1.^[7]

Further reading

• Krebs J, Klemenz R . The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis . Biochim. Biophys. Acta . 1498 . 2–3 . 153–61 . 2001 . 11108958 . 10.1016/S0167-4889(00)00091-4.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Vito P, Pellegrini L, Guiet C, D'Adamio L . Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction . J. Biol. Chem. . 274 . 3 . 1533–40 . 1999 . 9880530 . 10.1074/jbc.274.3.1533 . free .
• Tarabykina S, Møller AL, Durussel I, etal . Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition . J. Biol. Chem. . 275 . 14 . 10514–8 . 2000 . 10744743 . 10.1074/jbc.275.14.10514 . free .
• Chen B, Borinstein SC, Gillis J, etal . The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes . J. Biol. Chem. . 275 . 25 . 19275–81 . 2000 . 10858458 . 10.1074/jbc.M908994199 . free .
• Kitaura Y, Matsumoto S, Satoh H, etal . Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner . J. Biol. Chem. . 276 . 17 . 14053–8 . 2001 . 11278427 . 10.1074/jbc.M008649200 . free .
• Suzuki H, Fukunishi Y, Kagawa I, etal . Protein–Protein Interaction Panel Using Mouse Full-Length cDNAs . Genome Res. . 11 . 10 . 1758–65 . 2001 . 11591653 . 10.1101/gr.180101 . 311163 .
• Jung YS, Kim KS, Kim KD, etal . Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells . Biochem. Biophys. Res. Commun. . 288 . 2 . 420–6 . 2001 . 11606059 . 10.1006/bbrc.2001.5769 .
• Kitaura Y, Satoh H, Takahashi H, etal . Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions . Arch. Biochem. Biophys. . 399 . 1 . 12–8 . 2002 . 11883899 . 10.1006/abbi.2001.2736 .
• Satoh H, Shibata H, Nakano Y, etal . ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner . Biochem. Biophys. Res. Commun. . 291 . 5 . 1166–72 . 2002 . 11883939 . 10.1006/bbrc.2002.6600 .
• Chatellard-Causse C, Blot B, Cristina N, etal . Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization . J. Biol. Chem. . 277 . 32 . 29108–15 . 2002 . 12034747 . 10.1074/jbc.M204019200 . free .
• Hwang IS, Jung YS, Kim E . Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation . FEBS Lett. . 529 . 2–3 . 183–7 . 2002 . 12372597 . 10.1016/S0014-5793(02)03329-X . 9264865 . 2002FEBSL.529..183H .
• Satoh H, Nakano Y, Shibata H, Maki M . The penta-EF-hand domain of ALG-2 interacts with amino-terminal domains of both annexin VII and annexin XI in a Ca2+-dependent manner . Biochim. Biophys. Acta . 1600 . 1–2 . 61–7 . 2002 . 12445460 . 10.1016/S1570-9639(02)00445-4.
• Krebs J, Saremaslani P, Caduff R . ALG-2: a Ca2+ -binding modulator protein involved in cell proliferation and in cell death . Biochim. Biophys. Acta . 1600 . 1–2 . 68–73 . 2002 . 12445461 . 10.1016/S1570-9639(02)00446-6.
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Tomsig JL, Snyder SL, Creutz CE . Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif . J. Biol. Chem. . 278 . 12 . 10048–54 . 2003 . 12522145 . 10.1074/jbc.M212632200 . free .
• Hansen C, Tarabykina S, la Cour JM, etal . The PEF family proteins sorcin and grancalcin interact in vivo and in vitro . FEBS Lett. . 545 . 2–3 . 151–4 . 2003 . 12804766 . 10.1016/S0014-5793(03)00518-0 . 42572647 . 2003FEBSL.545..151H .

Notes and References

1. Vito P, Lacana E, D'Adamio L . Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3 . Science . 271 . 5248 . 521–5 . February 1996. 8560270 . 10.1126/science.271.5248.521 . 1996Sci...271..521V. 22286752 .
2. Web site: Entrez Gene: PDCD6 programmed cell death 6.
3. Hwang . In-Sik . Jung Yong-Sam . Kim Eunhee . October 2002. Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation . FEBS Lett. . 529 . 2–3 . 183–7 . Netherlands. 0014-5793. 12372597 . 10.1016/S0014-5793(02)03329-X . 9264865 . 2002FEBSL.529..183H .
4. Vito . P . Pellegrini L . Guiet C . D'Adamio L . January 1999. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction . J. Biol. Chem. . 274 . 3 . 1533–40 . UNITED STATES. 0021-9258. 9880530 . 10.1074/jbc.274.3.1533 . free .
5. Satoh . Hirokazu . Shibata Hideki . Nakano Yoshimi . Kitaura Yasuyuki . Maki Masatoshi . March 2002. ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner . Biochem. Biophys. Res. Commun. . 291 . 5 . 1166–72 . United States. 0006-291X. 11883939 . 10.1006/bbrc.2002.6600 .
6. Jung . Y S . Kim K S . Kim K D . Lim J S . Kim J W . Kim E . October 2001. Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells . Biochem. Biophys. Res. Commun. . 288 . 2 . 420–6 . United States. 0006-291X. 11606059 . 10.1006/bbrc.2001.5769 .
7. Kitaura . Y . Matsumoto S . Satoh H . Hitomi K . Maki M . April 2001. Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner . J. Biol. Chem. . 276 . 17 . 14053–8 . United States. 0021-9258. 11278427 . 10.1074/jbc.M008649200 . free .