TY - JOUR
T1 - Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and nuclear proteins
AU - Nakano, Satoshi
AU - Engel, Andrew G.
AU - Akiguchi, Ichiro
AU - Kimura, Jun
PY - 1997/8
Y1 - 1997/8
N2 - The pathological process in myofibrillar myopathy (MFM) (previously also referred to as 'desmin storage' or 'intermediate filament myopathy') results in dissolution of myofibrils, accumulation of products of the degradative process, and abnormal ectopic expression of desmin, dystrophin, gelsolin, NCAM, and N-terminal components of β-amyloid precursor protein. We now demonstrate that the abnormal fiber regions in MFM immunoreact strongly for (a) CDC2 kinase, the mitotic kinase that phosphorylates and disassembles intermediate filaments; (b) cyclin-dependent kinases CDK2, CDK4, and CDK7, which are involved in regulation of the cell cycle; (e) lamin B, which normally supports the inner nuclear membrane; and (d) the nuclear matrix associated protein. The normal muscle fiber lies in a terminally differentiated state and is refractory to reentry into the cell cycle. The abnormal expression of multiple cyclin-dependent kinases in the terminally differentiated muscle fiber implies inappropriate activation of positive regulators of mitosis and may signal a mitotic catastrophe. The dissolution of myofibrils may be due to hyperphosphorylation occurring during this event.
AB - The pathological process in myofibrillar myopathy (MFM) (previously also referred to as 'desmin storage' or 'intermediate filament myopathy') results in dissolution of myofibrils, accumulation of products of the degradative process, and abnormal ectopic expression of desmin, dystrophin, gelsolin, NCAM, and N-terminal components of β-amyloid precursor protein. We now demonstrate that the abnormal fiber regions in MFM immunoreact strongly for (a) CDC2 kinase, the mitotic kinase that phosphorylates and disassembles intermediate filaments; (b) cyclin-dependent kinases CDK2, CDK4, and CDK7, which are involved in regulation of the cell cycle; (e) lamin B, which normally supports the inner nuclear membrane; and (d) the nuclear matrix associated protein. The normal muscle fiber lies in a terminally differentiated state and is refractory to reentry into the cell cycle. The abnormal expression of multiple cyclin-dependent kinases in the terminally differentiated muscle fiber implies inappropriate activation of positive regulators of mitosis and may signal a mitotic catastrophe. The dissolution of myofibrils may be due to hyperphosphorylation occurring during this event.
KW - Cyclin-dependent kinases
KW - Immunocytochemistry
KW - Lamin B
KW - Myopathy
KW - Nuclear matrix associated protein
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U2 - 10.1097/00005072-199708000-00002
DO - 10.1097/00005072-199708000-00002
M3 - Article
C2 - 9258254
AN - SCOPUS:0030839795
SN - 0022-3069
VL - 56
SP - 850
EP - 856
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 8
ER -