What is BIM in cancer?
Bim promotes anoikis of many tumor cells, such as lung cancer, breast cancer, osteosarcoma, and melanoma. Various chemotherapeutic agents use Bim as a mediating executioner of cell death. Hence, Bim suppression supports metastasis and chemoresistance.
How do BCL2 inhibitors work?
Anti-apoptotic members of the BCL-2 family prevent MOMP through two mechanisms: the binding and sequestration of the active forms of BAK and BAX, and/or the sequestration of the direct activators BH3-only proteins. By binding to BAX and BAK, anti-apoptotic proteins such as BCL-2 prevent them from oligomerizing [6].
Why do Bcl-2 inhibitors work and where should we use them in the clinic?
BCL-2 family proteins and their complex interactions regulate intrinsic apoptosis. BH3 profiling can determine cancer cells’ priming for cell death and anti-apoptotic dependencies. Cancer cells often acquire anti-apoptotic defense mechanisms against oncogenic stress and therapy.
What is BIM protein?
Bcl-2-like protein 11, commonly called BIM, is a protein that in humans is encoded by the BCL2L11 gene.
What is the role of bid in apoptosis?
Bid is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for death receptor-mediated apoptosis in many cell systems. Bid action has been proposed to involve the mitochondrial re-location of its truncated form, tBid, to facilitate the release of apoptogenic proteins like cytochrome c.
Why do cells undergo Anoikis?
As a barrier to metastasis, cells normally undergo an apoptotic process known as “anoikis,” a form of cell death due to loss of contact with the extracellular matrix or neighboring cells.
What does BCL-2 positive mean?
Samples with 50% or more malignant cells expressing BCL2 were defined as BCL2 positive. In all, 69 DLBCL cases were stained with CD10, BCL6 and MUM1 to determine cell of origin subtype by Hans criteria.
Is Venetoclax a BCL-2 inhibitor?
Venetoclax (ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor that represents the first approved agent of this class and is currently widely used in the treatment of chronic lymphocytic leukemia (CLL) as well as acute myeloid leukemia (AML).
What are BCL-2 inhibitors?
A selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), with potential pro-apoptotic and antineoplastic activities. Upon administration, Bcl-2 inhibitor BCL201 binds to and inhibits the activity of Bcl-2. This restores apoptotic processes in tumor cells.
What is BIM apoptosis?
BIM works in concert with other pro-apoptotic proteins, such as PUMA, BAD, BAX, and anti-apoptotic proteins, such as BCL2, BCLXL, and MCL1, to regulate cell death and survival essential to normal tissue homeostasis. The precise regulation of BIM expression has been shown to be essential to normal development [3, 4].
What are BH3-only proteins?
Abstract. BH3-only BCL-2 family proteins are effectors of canonical mitochondrial apoptosis. They discharge their pro-apoptotic functions through BH1–3 pro-apoptotic proteins such as BAX and BAK, while their activity is suppressed by BH1–4 anti-apoptotic BCL-2 family members.
What is caspase cascade?
Caspases are a family of cysteine proteases that act in concert in a cascade triggered by apoptosis signaling. The culmination of this cascade is the cleavage of a number of proteins in the cell, followed by cell disassembly, cell death, and, ultimately, the phagocytosis and removal of the cell debris.
What is the role of BIM in apoptosis?
Bim: a novel member of the Bcl-2 family that promotes apoptosis Certain members of the Bcl-2 family inhibit apoptosis while others facilitate this physiological process of cell death.
Is BIM a novel protein?
An expression screen for proteins that bind to Bcl-2 yielded a small novel protein, denoted Bim, whose only similarity to any known protein is the short (nine amino acid) BH3 motif … Certain members of the Bcl-2 family inhibit apoptosis while others facilitate this physiological process of cell death.
Does BIM bind to Bcl-2?
An expression screen for proteins that bind to Bcl-2 yielded a small novel protein, denoted Bim, whose only similarity to any known protein is the short (nine amino acid) BH3 motif shared by most Bcl-2 homologues. Bim provokes apoptosis, and the BH3 region is required for Bcl-2 binding and for most of its cytotoxicity.
Does BIM act as a’death ligand’?
Significantly, Bcl-xL and Bcl-w, the two closest homologues of Bcl-2, also bind to Bim and inhibit its activity, but more distant viral homologues, adenovirus E1B19K and Epstein-Barr virus BHRF-1, can do neither. Hence, Bim appears to act as a ‘death ligand’ which can only neutralize certain members of the pro-survival Bcl-2 sub-family.