8.A.69 The Pro-apoptotic Bcl-2-Family Protein Bim (Bim) Family 

The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax (Frank et al. 2015). Interactions of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM; TC# 3.A.8) have been documented. Protein receptors may be involved in the import process.  In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing, but the physiological role of the Bim-TOM-interaction remains unclear.



This family belongs to the Bcl-2 Superfamily.

 

References:

Frank, D.O., J. Dengjel, F. Wilfling, V. Kozjak-Pavlovic, G. H├Ącker, and A. Weber. (2015). The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM). PLoS One 10: e0123341.

Fukazawa, H., K. Noguchi, A. Masumi, Y. Murakami, and Y. Uehara. (2004). BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther 3: 1281-1288.

Marani, M., T. Tenev, D. Hancock, J. Downward, and N.R. Lemoine. (2002). Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol. Cell Biol. 22: 3577-3589.

O'Connor, L., A. Strasser, L.A. O'Reilly, G. Hausmann, J.M. Adams, S. Cory, and D.C. Huang. (1998). Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO. J. 17: 384-395.

Examples:

TC#NameOrganismal TypeExample
8.A.69.1.1

BH3-only protein, also called Bcl-2-like protein 11, Bim, of 198 aas and 1 C-terminal TMS; induces apoptosis and anoikis (Fukazawa et al. 2004). Different isoforms have differing activities (Marani et al. 2002). Isoform Bim-alpha3 induces apoptosis, possibly through a caspase-mediated pathway, but isoforms BimAC and BimABC lack the ability to induce apoptosis.

Bim of Homo sapiens

 
8.A.69.1.2

Bcl-2 interacting mediator of cell death of 176 aas and one C-terminal TMS.

Bim of Danio rerio (Zebrafish) (Brachydanio rerio)

 
8.A.69.1.3

Bcl-2-like protein 11 of 166 aas and 1 C-terminal TMS

Bcl-2-like protein of Callorhinchus milii (Ghost shark)