TY - JOUR
T1 - Mcl-1 regulation and its role in multiple myeloma
AU - Le Gouill, Steven
AU - Podar, Klaus
AU - Harousseau, Jean-Luc
AU - Anderson, Kenneth C
PY - 2004/10
Y1 - 2004/10
N2 - Among the Bcl-2 family, myeloid cell leukemia-1 (Mcl-1) distinguishes itself from the other pro-survival proteins by its ability to oppose to a wide variety of pro-apoptotic stimuli, short half-life, and presence of polypeptide sequences enriched in proline (P), glutamic acid (E), serine (S) and threonine (T) domains (PEST). Moreover, Mcl-1 undergoes a complex transcriptional, post-transcriptional, and post-translational regulation process. This regulation modifies not only Mcl-1 expression, but also its function. Various extra-cellular stimuli, including cytokines, growth factors, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and IFN, activate pathways which regulate Mcl-1 expression. Furthermore, Mcl-1 can be alternatively spliced into a long (Mcl-1) or a short (Mcl-1S) form. Mcl-1 opposes pro-apoptotic proteins and can be either cleaved or phosphorylated at a post-translational level. Mcl-1-spliced products, Mcl-1-cleaved products, or phosphorylated Mcl-1 have either a pro or an anti-apoptotic function, highlighting the complexity and pivotal role of Mcl-1 regulation. Here we discuss the regulation and function of Mcl-1 in the pathophysiology of multiple myeloma.
AB - Among the Bcl-2 family, myeloid cell leukemia-1 (Mcl-1) distinguishes itself from the other pro-survival proteins by its ability to oppose to a wide variety of pro-apoptotic stimuli, short half-life, and presence of polypeptide sequences enriched in proline (P), glutamic acid (E), serine (S) and threonine (T) domains (PEST). Moreover, Mcl-1 undergoes a complex transcriptional, post-transcriptional, and post-translational regulation process. This regulation modifies not only Mcl-1 expression, but also its function. Various extra-cellular stimuli, including cytokines, growth factors, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and IFN, activate pathways which regulate Mcl-1 expression. Furthermore, Mcl-1 can be alternatively spliced into a long (Mcl-1) or a short (Mcl-1S) form. Mcl-1 opposes pro-apoptotic proteins and can be either cleaved or phosphorylated at a post-translational level. Mcl-1-spliced products, Mcl-1-cleaved products, or phosphorylated Mcl-1 have either a pro or an anti-apoptotic function, highlighting the complexity and pivotal role of Mcl-1 regulation. Here we discuss the regulation and function of Mcl-1 in the pathophysiology of multiple myeloma.
KW - Exons/genetics
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Interleukin-6/metabolism
KW - Multiple Myeloma/metabolism
KW - Myeloid Cell Leukemia Sequence 1 Protein
KW - Neoplasm Proteins/chemistry
KW - Proto-Oncogene Proteins c-bcl-2/chemistry
KW - Vascular Endothelial Growth Factor A/metabolism
UR - http://www.scopus.com/inward/record.url?scp=13944274500&partnerID=8YFLogxK
U2 - 10.4161/cc.3.10.1196
DO - 10.4161/cc.3.10.1196
M3 - Review article
C2 - 15467463
SN - 1538-4101
VL - 3
SP - 1259
EP - 1262
JO - Cell Cycle
JF - Cell Cycle
IS - 10
ER -