Regulation of Protein Transport to the Nucleus: Central Role of
Phosphorylation.
Jans, David A., and Stefan Hbner.
Nuclear Signalling Laboratory, Division for Biochemistry and Molecular
Biology, John Curtin School of medical Research, Australian National
University, Canberra, Australia.
APStracts 2:0009P, 1996.
ABSTRACT
Nuclear protein transport is integral to eukaryotic cell processes such as
differentiation, transformation, and the control of gene expression. Whilst
the targeting role of nuclear localization signals (NLSs) has been known for
some time, more recent results indicate that NLS-dependent nuclear protein
import is precisely regulated. Phosphorylation appears to be the main
mechanism controlling the nuclear transport of a number of proteins, including
transcription factors such as NF[kappa]B, c-[i]rel[r], [i]dorsal[r], and SWI5
from yeast. Cytoplasmic retention factors, intra- and intermolecular NLS
masking, and NLS masking by phosphorylation are some of the mechanisms by
which phosphorylation specifically regulates nuclear transport. Even nuclear
localization of the archetypal NLS-containing simian virus 40 large tumor
antigen (T-ag) is regulated, namely by the "CcN motif," which comprises the T-
ag NLS ("N") determining ultimate subcellular destination, a casein kinase II
site ("C") 13 amino acids NH[inf]2[r]-terminal to the NLS modulating the rate
of nuclear import, and a cyclin-dependent kinase site ("c") adjacent to the
NLS regulating the maximal level of nuclear accumulation. The CcN motif
appears to be a special form of phosphorylation-regulated NLS (prNLS), where
phosphorylation at site(s) close to the NLS specifically regulates NLS
function. The regulation of nuclear transport through phosphorylation and
prNLSs appears to be common in eukaryotic cells from yeast and plants to
higher mammals.
APS Manuscript Number P2-6.
Article publication pending July 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96