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Vol. 12, Issue 1, 73-83, January 2001
and
*Department of Cell and Molecular Biology, Umeå University, S-901
87 Umeå, Sweden; and Oncoprotein18/stathmin (Op18) is a microtubule (MT) destabilizing
protein that is inactivated during mitosis by phosphorylation at four
Ser-residues. Op18 has at least two functions; the N-terminal region is
required for catastrophe-promotion (i.e., transition from elongation to
shortening), while the C-terminal region is required to inhibit
MT-polymerization rate in vitro. We show here that a
"pseudophosphorylation" derivative of Op18 (i.e., four Ser- to
Glu-substitutions at phosphorylation sites) exhibits a selective loss
of catastrophe-promoting activity. This is contrasted to authentic
phosphorylation, which efficiently attenuates all activities except
tubulin binding. In intact cells, overexpression of
pseudophosphorylated Op18, which is not phosphorylated by endogenous kinases, is shown to destabilize interphase MTs but to leave spindle formation untouched. To test if the mitotic spindle is sensitive only
to the catastrophe-promoting activity of Op18 and resistant to
C-terminally associated activities, N- and C-terminal truncations with
defined activity-profiles were employed. The cell-cycle phenotypes of
nonphosphorylatable mutants (i.e., four Ser- to Ala-substitutions) of
these truncation derivatives demonstrated that catastrophe promotion is
required for interference with the mitotic spindle, while the
C-terminally associated activities are sufficient to destabilize
interphase MTs. These results demonstrate that specific Op18
derivatives with defined activity-profiles can be used as probes to
distinguish interphase and mitotic MTs.
Department of Biological
Sciences, Lehigh University, Bethlehem, Pennsylvania 18015
Present address: Dept. of Biology, University of
North Carolina, Chapel Hill, NC 27599.
§
These authors contributed equally to this work and
are listed in alphabetical order
¶
Corresponding author. E-mail address:
Martin.Gullberg{at}cmb.umu.se.
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