Characterization of a Novel 350-Kilodalton Nuclear Phosphoprotein That Is Specifically Involved in Mitotic-Phase Progression

Abstract

A gene assigned to human chromosome 1q32-41 encodes a novel protein of 3,113 amino acids containing an internal tandem repeat of 177 amino acids. The protein, which we have named ''mitosin,'' was identified by direct binding to purified retinoblastoma protein in vitro with a region distantly related to the retinoblastoma protein-binding site of E2F-1. Mitosin is expressed throughout S, G 2 , and M phases of the cell cycle but is absent in G 1 . Its localization is dramatically reorganized from a rather homogeneous nuclear distribution in S phase to paired dots at the kinetochore/centromere region, to the spindle apparatus, and then to the midbody during M-phase progression. This spatial reorganization coincides closely with the temporal phosphorylation patterns of mitosin. Overexpression of N-terminally truncated mutants blocks cell cycle progression mainly at G 2 /M. These results suggest that mitosin may play an important role in mitotic-phase progression.

Polyomavirus large T antigen-dependent DNA amplification

“…Downstream targets of p53 at the G 2 control are not known so far. On the other hand, the observations that pRB interacts with several proteins potentially involved in mitosis Zhu et al, 1995;Thomas et al, 1996) as well as the fact that pRB exhibits M phase-speci®c binding to a protein phosphatase type 1 which may be related to cell cycle-speci®c changes of the phosphorylation status of pRB (Durfee et al, 1993) is of particular interest. It is possible that PyLT interferes with such functions of pRB resulting in failures during mitosis.…”

Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway

“…Our laboratory has studied the structure, expression, and function of LEK1, a relatively large murine protein (Ͼ300 kDa) highly related to CMF1 (chicken) and CENP-F͞mitosin (human) (16,17). These proteins share a similar domain structure comprised of a cluster of leucine zippers in the N terminus, a central spectrin repeat, and a nuclear localization sequence along with an atypical retinoblastoma-binding domain in the C terminus (18)(19)(20).…”

Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins

“…The C-terminal half of Evi5 shows signi®cant homology to a number of coiled-coil proteins including mitosin, a protein involved in cell cycle control (Liao et al, 1995a;Zhu et al, 1995). Mitosin is a *350 kDa nuclear phosphoprotein that is expressed only during the S and G 2 /M phases of the cell cycle.…”

“…The C-terminal region of Evi5 shows signi®cant homology to a number of coiled-coil proteins including several myosin heavy chain proteins and mitosin (also called CENP-F), a novel *350-kilodalton nuclear phosphoprotein involved in regulating mitotic-phase cell cycle progression (Zhu et al, 1995;Liao et al, 1995b). Proviral integrations at the Evi5 locus are located within the coding region of the Evi5 gene Two mouse genomic lambda clones (lg2 and lg4, Figure 1) that span the entire Evi5 common integration site (Liao et al, 1995a) were used to determine the location and orientation of proviral integrations with respect to the Evi5 gene.…”