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J. Biol. Chem., Vol. 275, Issue 37, 28888-28892, September 15, 2000
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From the The Ki-67 antigen (pKi-67) is widely used as a
cell proliferation marker protein. Its actual role in the cell cycle
progression, however, is presently unclear. Using a two-hybrid
screening in yeast, a novel protein, termed Hklp2 (human
kinesin-like protein 2), was identified and shown to interact with the
forkhead-associated (FHA) domain of pKi-67. Hklp2 has 1388 amino acids
and shows a striking similarity (a 53% identity in amino acids) to
Xklp2, a plus-end directed kinesin-like motor found in
Xenopus. The interaction domain of Hklp2 was mapped to the
portion that comprised residues 1017-1237 and that was phosphorylated
in vitro by incubating with mitotic but not interphasic
HeLa cell extracts. That the interaction was striking in the mitotic
extract was also verified. In addition, immunofluorescence using
specific antibodies revealed an association between pKi-67 and Hklp2 at
the periphery of mitotic chromosomes, largely in close proximity to the
centromeres. These findings suggest that pKi-67 is involved in the
progression of mitosis via its interaction with Hklp2.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AB035898.
The Forkhead-associated Domain of Ki-67 Antigen Interacts
with the Novel Kinesin-like Protein Hklp2*
§,¶
Department of Cell Biology and Neuroscience,
Graduate School of Medicine, Osaka University, 2-2 Yamada-oka,
Suita, Osaka 565-0871, Japan and the ¶ Institute for Molecular and
Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita,
Osaka 565-0871, Japan
*
This work was supported by Grant-in-Aid for Scientific
Research on Priority Areas (B) 11237202 and Grant-in-Aid for COE
Research 07CE2006 from the Japanese Ministry of Education, Science,
Sports and Culture and by funds from the Mitsubishi Foundation and the Human Frontiers Science Program.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
81-6-6879-3210; Fax: 81-6-6879-3219; E-mail:
yyoneda@anat3.med.osaka-u.ac.jp.
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