BAG4 explained

BAG family molecular chaperone regulator 4 is a protein that in humans is encoded by the BAG4 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. The regulatory role of this protein in cell death was demonstrated in epithelial cells which undergo apoptosis while integrin mediated matrix contacts are lost.

Interactions

BAG4 has been shown to interact with:

• APOBEC1,^[4]
• HSPA8,^[5] and
• TNFRSF1A.^[5]

Further reading

• Riley BM . A Genome-Wide Linkage Scan for Cleft Lip and Cleft Palate Identifies a Novel Locus on 8p11-23 . Am. J. Med. Genet. A . 143 . 8 . 846–52 . 2007 . 17366557 . 10.1002/ajmg.a.31673 . 2570349 . vanc. Schultz RE . Cooper ME . 3 . Goldstein-Mchenry . T. . Daack-Hirsch . S. . Lee . K.T. . Dragan . E. . Vieira . A.R. . Lidral . A.C. .
• Yang ZQ . Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer . Cancer Res. . 66 . 24 . 11632–43 . 2007 . 17178857 . 10.1158/0008-5472.CAN-06-2946 . vanc. Streicher KL . Ray ME . 3 . Abrams . J. . Ethier . S. P. . free .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . vanc. Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Lau PP, Chan L . Involvement of a chaperone regulator, Bcl2-associated athanogene-4, in apolipoprotein B mRNA editing . J. Biol. Chem. . 278 . 52 . 52988–96 . 2004 . 14559896 . 10.1074/jbc.M310153200 . free .
• Al-Lamki RS . Expression of Silencer of Death Domains and Death-Receptor-3 in Normal Human Kidney and in Rejecting Renal Transplants . Am. J. Pathol. . 163 . 2 . 401–11 . 2003 . 12875962 . 10.1016/S0002-9440(10)63670-X. 1868232 . vanc. Wang J . Thiru S . 3 . Pritchard . NR . Bradley . JA . Pober . JS . Bradley . JR .
• Eichholtz-Wirth H, Fritz E, Wolz L . Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways . Cancer Lett. . 194 . 1 . 81–9 . 2003 . 12706861 . 10.1016/S0304-3835(03)00009-0 .
• Strausberg RL . 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 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Briknarová K . BAG4/SODD protein contains a short BAG domain . J. Biol. Chem. . 277 . 34 . 31172–8 . 2002 . 12058034 . 10.1074/jbc.M202792200 . vanc. Takayama S . Homma S . 3 . Baker . K . Cabezas . E . Hoyt . DW . Li . Z . Satterthwait . AC . Ely . KR . free .
• Eichholtz-Wirth H, Sagan D . Altered signaling of TNFalpha-TNFR1 and SODD/BAG4 is responsible for radioresistance in human HT-R15 cells . Anticancer Res. . 22 . 1A . 235–40 . 2002 . 12017295 .
• Antoku K . Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein . Biochem. Biophys. Res. Commun. . 286 . 5 . 1003–10 . 2001 . 11527400 . 10.1006/bbrc.2001.5512 . vanc. Maser RS . Scully WJ . 3 . Delach . Scott M. . Johnson . Daniel E. .
• Frisch SM . Evidence for a function of death-receptor-related, death-domain-containing proteins in anoikis . Curr. Biol. . 9 . 18 . 1047–9 . 2000 . 10508612 . 10.1016/S0960-9822(99)80455-2 . 17212216 . free .

Notes and References

1. Takayama S, Xie Z, Reed JC . An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators . J Biol Chem . 274 . 2 . 781–6 . Feb 1999 . 9873016 . 10.1074/jbc.274.2.781 . free .
2. Jiang Y, Woronicz JD, Liu W, Goeddel DV . Prevention of constitutive TNF receptor 1 signaling by silencer of death domains . Science . 283 . 5401 . 543–6 . Feb 1999 . 9915703 . 10.1126/science.283.5401.543 . 1999Sci...283..543J .
3. Web site: Entrez Gene: BAG4 BCL2-associated athanogene 4.
4. Dec 2003 . Lau PP, Chan L . Involvement of a chaperone regulator, Bcl2-associated athanogene-4, in apolipoprotein B mRNA editing . J. Biol. Chem. . 278 . 52 . 52988–96 . 14559896 . 10.1074/jbc.M310153200. free .
5. Apr 2002 . Miki K, Eddy EM . Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain . Mol. Cell. Biol. . 22 . 8 . 2536–43 . 11909948 . 133739 . 10.1128/MCB.22.8.2536-2543.2002.