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BIOLOGICAL SCIENCES / CELL BIOLOGY
A mammalian NudC-like protein essential for dynein stability and cell viability
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
Contributed by Raymond L. Erikson, April 27, 2006
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 
-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.
chaperone | mitosis | proteasome | degradation | aggregation
Present address: Department of Biochemistry, Purdue University, West Lafayette, IN 47907.
Author contributions: T.Z., W.Z., and R.L.E. designed research; T.Z. and W.Z. performed research; X.L. contributed new reagents/analytic tools; T.Z., W.Z., X.L., and R.L.E. analyzed data; and T.Z., W.Z., and R.L.E. wrote the paper.
Conflict of interest statement: No conflicts declared.
To whom correspondence should be addressed. E-mail: erikson{at}mcb.harvard.edu
© 2006 by The National Academy of Sciences of the USA
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