BAG6, alternately known as BAT3, was originally identified as a gene within the class III region of the human major histocompatibility complex, but has subsequently been found to exhibit protein chaperone activity. BAG6, in conjunction with other chaperone proteins and ubiquitin ligases, regulates protein stability and insertion of tail-anchored membrane proteins into the endoplasmic reticulum. The BAT3 complex, consisting of BAG6, TRC35, and Ubl4a localizes to ribosomes synthesizing membrane proteins and facilitates tailed-anchored protein capture by TRC40 and subsequent insertion of the nascent protein in to the ER membrane. BAG6 also plays a critical role in clearing cells of mis-folded and mis-localized peptides via ER-associated degradation and the ubiquitin-proteasome system. BAG6 may also act as a chaperone for glycoproteins through its interaction with DERLIN2.In addition to its role as a chaperone, BAG6 has also been implicated in regulating chromatin structure and gene expression. For example, BAG6 and SET1A act as binding partners for BORIS to effect changes of chromatin structure and gene expression. Similarly, increased expression of BAG6 induces p300-mediated acetylation of p53, which is required for DNA damage response. BAG6 has also been found to interact with TGF-β, and in so doing acts as a positive regulator of TGF-β1 stimulation of type 1 collagen expression. BAG6 also suppresses bone morphogenic protein signaling via its interaction with and regulation of small C-terminal domain phosphatase that dephosphorylates SMAD proteins, resulting in subsequent termination of BMP-mediated events.
[1] Hessa, T. et al. (2011) Nature 475, 394-7.
[2] David, R. (2011) Nat Rev Mol Cell Biol 12, 550.
[3] Ast, T. and Schuldiner, M. (2011) Curr Biol 21, R692-5.
[4] Mariappan, M. et al. (2010) Nature 466, 1120-4.
[5] Leznicki, P. et al. (2010) J Cell Sci 123, 2170-8.
[6] Minami, R. et al. (2010) J Cell Biol 190, 637-50.
[7] Wang, Q. et al. (2011) Mol Cell 42, 758-70.
[8] Claessen, J.H. and Ploegh, H.L. (2011) PLoS One 6, e28542.
[9] Nguyen, P. et al. (2008) Mol Cell Biol 28, 6720-9.
[10] Sasaki, T. et al. (2007) Genes Dev 21, 848-61.
