Interaction between RB protein and Nu MA is required for proper alignment of spindle microtubules

Retinoblastoma protein (p RB ) controls cell cycle progression and cell cycle exit through interactions with cellular proteins. Many p RB ‐binding proteins, which function in gene transcription or modulation of chromatin structure, harbor LXCXE motifs in their binding domain for p RB . In this study, we found that nuclear mitotic apparatus protein ( N u MA ), a mitotic spindle organizer, interacts with p RB through LSCEE sequences located in its C ‐terminal region. si RNA ‐mediated down‐regulation of p RB caused aberrant distribution of N u MA and alignment of spindle microtubules in mitotic cells. Abnormal organization of spindle microtubules was also accompanied by misalignment of an over‐expressed N u MA mutant (mut‐ N u MA ) with a defect in p RB binding caused by an LSGEK mutation. The mut‐ N u MA ‐over‐expressing cells showed lower potency for survival than wild‐type N u MA (wt‐ N u MA )‐over‐expressing cells during 2 weeks of culture. Interestingly, knockdown of p RB reduced the population of wt‐ N u MA ‐over‐expressing cells to the same level as mut‐ N u MA cells after 2 weeks. Taken together, p RB may have a novel function in regulating the mitotic function of N u MA and spindle organization, which are required for proper cell cycle progression.