Phospho-MCL-1 (Ser159) Monoclonal Antibody (RBCERNR), APC, eBioscience™, Invitrogen™

Description

• This RBCERNR MAb recognizes human and mouse myeloid cell leukemia sequence 1 (Mcl-1) when phosphorylated on serine 159 (S159)
• Mcl-1 is an anti-apoptotic protein that is a member of the Bcl-2 family of proteins important for regulation of cell survival/apoptosis
• Mcl-1 is primarily localized to the outer membrane of mitochondria where it prevents cytochrome c release via dimerization with other Bcl-2 family members such as Bim
• PI3K activation of AKT results in the phosphorylation of GSK3 beta at serine 9 (S9) resulting in destabilization and degradation of GSK3 beta
• Loss of GSK3 beta prevents phosphorylation of Mcl-1 on S159 and its subsequent ubiquitnation and degradation
• Mice conditionally lacking Mcl-1 in lymphocytes showed that Mcl-1 is essential during early lymphoid development and for the maintenance of mature lymphocytes
• MCL1 (Myeloid cell leukemia-1) belongs to the Bcl-2 family and is involved in programing, differentiation and concomitant maintenance of cell viability, but not of proliferation
• Isoform 1 of MCL1 inhibits apoptosis while isoform 2 promotes it
• The carboxy terminal of MCL1 and bcl-2 share significant sequence homology
• Expression of MCL1 is increased upon exposure of ML-1 cells to various types of DNA damaging agents (e.g
• ionizing radiation, μgtraviolet radiation, and alkylating drugs) along with increases in GADD45 and Bax and a decrease in bcl-2
• Enhanced expression of MCL1, prominently associated with mitochondria, complements the continued expression of bcl-2 in ML-1 cells undergoing differentiation
• Like bcl-2, MCL1 has the capacity to promote cell viability under conditions that otherwise cause apoptosis
• While the mechanism by which MCL1 inhibits apoptosis is not known, it is thought that it may heterodimerize and neutralize pro-apoptotic members of the Bcl-2 family such as Bim or Bak
• MCL1 was originally identified in differentiating myeloid cells, but has since been shown to be expressed in multiple cell types
• MCL1 is essential for embryogenesis and for the development and maintenance of B and T lymphocytes in animals
• MCL1 exists as at least two distinct isoforms designated MCL1L and MCL1S
• In marked contrast to the larger isoform of MCL1, overexpression of MCL1S promotes cell death.