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ISABEL ÁLVAREZ-TABARÉS Y COLS. ANAL. REAL ACAD. NAC. FARM.

POSSIBLE FUNCTIONS OF DIS2 AND SDS21
IN THE NUCLEUS

While PP1 has been found in the nucleus of all organisms, there
are differences between the localisation of specific isoforms and cell
cycle stages between organisms. In mammalian cells, fluorescence
microscopy revealed specific and distinct in vivo localisation patterns
for PP1a-GFP, PP1ß/d-GFP and PP1?-GFP (14). These localisations
agreed with immunolocalisation data shown for endogenous
isoforms using anti-peptide antibodies specific for each isoform (29).
In S. cerevisiae, GFP-Glc7 localises in the nucleus throughout the
mitotic cell cycle, and is enriched in the nucleolus (30). Finally,
BIMG-GFP, in Aspergillus nidulans, also localises to the nucleus.
However, its localisation is dependent upon nutritional conditions;
on a poor growth medium, BIMG-GFP shows a greater affinity for
the nucleolus than the nucleoplasm, whereas on rich medium, it is
more evenly distributed between the two nuclear regions (31). PP1
also changes its distribution in response to nutritional conditions in
mammalian tissue cultures, where PP1 is located primarily in the
cytoplasm in quiescent cells, but accumulates in the nucleus upon
addition of serum and entry into the mitotic cell cycle (32). Likewise,
in budding yeast, GFP-Glc7 is uniformly dispersed throughout the
cell in stationary phase (33). In the case of PP1 in S. pombe, changes
in Dis2 and Sds21 nuclear localisation have not been observed in
response to different nutritional conditions.

Not much is known about the possible roles for PP1 in the
nucleolus. An Aspergillus nidulans PP1 mutant, bimG11, has
hyperphosphorylated nucleolar proteins, supporting the idea that
substrates for PP1 are found in the nucleolus (34). In contrast to the
uncertainty about the possible role of PP1 in the nucleolus, many
studies have linked PP1 function to key nuclear processes such as
cell-cycle progression, replication, transcription and RNA processing.

One of the most supported roles for chromatin-associated PP1 is
the reversal of signalling by protein kinases of the Aurora family.
One of the mitotic substrates of Aurora kinases is histone H3, which
is phosphorylated on serine 10 (Ser 10) by the unique Aurora protein
kinase in budding yeast, IplI (35) and in fission yeast, Ark1 (36), and
Aurora B protein kinase in Drosophila (37). Various studies have

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