The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing.[7] The protein MCL1 has a very short biological half-life of only 20–30 minutes.[8]
The loss of MCL1 has a more dramatic impact than the loss of any other anti-apoptotic member of the Bcl-2 family. Loss of the Mcl-1 gene results in embryo death when the embryo is only around 3.5 days old, before it has even implanted. Conditional deletion of Mcl-1 depletes a wide variety of cells, including hematopoietic stem cells, B cell–committed progenitors, T cell–committed progenitors, antibody-secreting plasma cells, cardiac muscle cells, and neurons.[8] Deletion of Mcl-1 in hepatocytes causes apoptosis and aberrant polyploidization but improves liver regeneration after surgery.[9][10] MCL1 works synergistically with p53 in protecting liver from injury, fibrosis and cancer.[11]
Omacetaxine mepesuccinate (a drug approved for the treatment for chronic myelogenous leukemia) and Seliciclib[12] (which is under investigation as a potential multiple myeloma treatment) both act in part by inhibiting synthesis of Mcl-1. MCL1 has been identified as a resistance factor for BCL-2 inhibitor venetoclax in lymphoma cells. Therefore, new strategies of combining BCL-2 and MCL1 inhibitors are currently under clinical trials for several tumor types.[13]
^Weng SY, Yang CY, Li CC, Sun TP, Tung SY, Yen JJ, et al. (April 2011). "Synergism between p53 and Mcl-1 in protecting from hepatic injury, fibrosis and cancer". Journal of Hepatology. 54 (4): 685–694. doi:10.1016/j.jhep.2010.07.035. PMID21146511.
^MacCallum DE, Melville J, Frame S, Watt K, Anderson S, Gianella-Borradori A, et al. (June 2005). "Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1". Cancer Research. 65 (12): 5399–5407. doi:10.1158/0008-5472.CAN-05-0233. PMID15958589.
^Leu JI, Dumont P, Hafey M, Murphy ME, George DL (May 2004). "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex". Nature Cell Biology. 6 (5): 443–450. doi:10.1038/ncb1123. PMID15077116. S2CID43063712.
^Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–330. doi:10.1023/A:1011319901057. PMID11483855. S2CID23119757.
^Makishima T, Yoshimi M, Komiyama S, Hara N, Nishimoto T (September 2000). "A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1, one of the bcl-2 protein family". Journal of Biochemistry. 128 (3): 399–405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID10965038.
Overview of all the structural information available in the PDB for UniProt: Q07820 (Induced myeloid leukemia cell differentiation protein Mcl-1) at the PDBe-KB.
PDB gallery
2nl9: Crystal structure of the Mcl-1:Bim BH3 complex
2nla: Crystal structure of the Mcl-1:mNoxaB BH3 complex
One thought on “Cannabaceae”
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction