Research led by St. Jude Children's Research Hospital investigators suggests that safeguarding cell survival and maintaining a balanced immune system is just the start of the myeloid cell leukemia sequence 1 (MCL1) protein's work.
Nearly 20 years after MCL1 was discovered, scientists have identified a second form of the protein that works in a different location in cells and performs a different function. This newly identified version is shorter and toils inside rather than outside mitochondria where it assists in production of chemical energy that powers cells. The research appears in today's online edition of the scientific journal Nature Cell Biology.
The finding will likely aid the development of cancer drugs. Many cancers feature high levels of MCL1 or extra copies of the gene, and there is widespread interest in the protein for its potential to treat cancer. Until now, however, those efforts have focused solely on MCL1's role on the outer mitochondrial membrane, where it blocks cell death via the apoptotic or cell suicide pathway. This study highlights another role.
"We believe this newly identified form of MCL1 that works inside the mitochondria is probably essential for tumor cell survival. If that proves to be correct, then strategies to block the protein from getting into mitochondria offer a new therapeutic approach for cancer treatment," said Joseph Opferman, Ph.D., an associate member of the St. Jude Department of Biochemistry and a Pew Scholar in the Biomedical Sciences. He is the paper's senior author.
Opferman has a longstanding interest in MCL1, which belongs to the BCL2 family of proteins that are critical regulators of apoptosis. Unlike other BCL2 proteins, MCL1 is required for embryonic development and for the survival of a variety of normal cell types. The protein is also essential for cancer cell survival.
Until now, however, researchers were unsure how to reconcile MCL1's varied roles wi
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St. Jude Children's Research Hospital