A mammalian NudC-like protein essential for dynein stability and cell viability.
Cytoplasmic dynein, a minus-end-directed microtubule motor, has been implicated in many fundamental cellular processes; however, little is known regarding the underlying molecular machinery that regulates its stability. In Aspergillus nidulans, nuclear distribution gene C (nudC) has been implicated in the regulation of dynein-mediated nuclear migration. Here, we characterize a previously undescribed mammalian NudC-like protein (NudCL). The expression and phosphorylation of NudCL are increased during mitosis. Depletion of NudCL by RNA interference in HeLa cells inhibits cell growth and induces mitotic arrest with multiple mitotic defects, which subsequently result in cell death. Unexpectedly, the majority of NudCL depletion-induced mitotic defects may result from loss of dynein function; this interpretation is supported by the failure to recruit sufficient gamma-tubulin to spindle poles and the mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles during mitosis. Depletion of NudCL also results in the aggregation of dynein intermediate chain throughout the cytoplasm during mitosis. NudCL was shown to bind to the dynein complex, and its depletion induces degradation of dynein intermediate chain, a process suppressed by MG132, a proteasome inhibitor. Taken together, these data suggest a previously undescribed mechanism whereby NudCL appears to influence the stabilization of dynein intermediate chain.
Zhou
Tianhua
T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Zimmerman
Wendy
W
Liu
Xiaoqi
X
Erikson
Raymond L
RL
D000818:Animals; D001233:Aspergillus nidulans / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival; D004398:Dyneins / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D007976:Leupeptins; C512648:NUDC protein, human; C513128:NUDCD3 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D004398:Dyneins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde