Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer's disease pathology.
The anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase complex that functions in regulating cell cycle transitions in proliferating cells and has, as revealed recently, novel roles in postmitotic neurons. Regulated by its activator Cdh1 (or Hct1), whose level is high in postmitotic neurons, APC/C seems to have multiple functions at different cellular locations, modulating diverse processes such as synaptic development and axonal growth. These processes do not, however, appear to be directly connected to cell cycle regulation. It is now shown that Cdh1-APC/C activity may also have a basic role in suppressing cyclin B levels, thus preventing terminally differentiated neurons from aberrantly re-entering the cell cycle. The result of an aberrant cyclin B-induced S-phase entry, at least for some of these neurons, would be death via apoptosis. Cdh1 thus play an active role in maintaining the terminally differentiated, non-cycling state of postmitotic neurons--a function that could become impaired in Alzheimer's and other neurodegenerative diseases.
Aulia
Selina
S
Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
Tang
Bor Luen
BL
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D064173:Anaphase-Promoting Complex-Cyclosome; D017209:Apoptosis / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D064200:Cdh1 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; C577584:FZR1 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase