PMID- 10602474
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 51
DP  - 1999 Dec 2
TI  - C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport 
      and high apoptotic activity.
PG  - 7212-8
AB  - Dlk (also termed ZIP kinase) is a novel serine/threonine kinase with a unique
      C-terminal domain that is rich in arginine and contains three putative NLS motifs
      and a functional lecuine zipper. Dlk is indeed localized in the nucleus where it 
      shows a speckled distribution. To elucidate the biological functions of Dlk, we
      wanted to identify the signals relevant for nuclear transport and further the
      nuclear structures which Dlk binds to. Expression of various deletion and point
      mutations of Dlk as GFP fusion proteins revealed that the leucine zipper is
      required for association with speckles and the most C-terminal NLS is necessary
      and sufficient for nuclear transport. Interestingly, a C-terminal deletion mutant
      defective for nuclear transport exhibited a pronounced colocalization with actin 
      filaments and, even more strikingly, was a very potent inducer of apoptosis. This
      apoptotic activity was abrogated, however, when this mutant was retargeted to the
      nucleus via a heterologous NLS from large T, indicating that Dlk only exerts an
      apoptotic activity in the cytoplasm. To identify the speckle like structures to
      which Dlk binds we performed immunofluorescence analyses with antibodies directed
      against representative marker proteins of replication, transcription, or splicing
      centers. None of these marker proteins revealed a colocalization with Dlk.
      Instead, we found a partial colocalization with PML bodies which seem to play a
      key role in regulation of apoptosis. Taken together, these data strongly suggest 
      a functional role for Dlk in control of cell survival which is dependent on its
      subcellular localization.
FAU - Kogel, D
AU  - Kogel D
AD  - Institute of Genetics, University of Bonn, Roemerstr. 164, D-53117 Bonn, Germany.
FAU - Bierbaum, H
AU  - Bierbaum H
FAU - Preuss, U
AU  - Preuss U
FAU - Scheidtmann, K H
AU  - Scheidtmann KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Apoptosis Regulatory Proteins
MH  - Biological Transport/genetics
MH  - Calcium-Calmodulin-Dependent Protein Kinases
MH  - Cell Line
MH  - Cell Nucleus/*physiology
MH  - Death-Associated Protein Kinases
MH  - Leucine Zippers
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/*physiology
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203169 [doi]
PST - ppublish
SO  - Oncogene. 1999 Dec 2;18(51):7212-8. doi: 10.1038/sj.onc.1203169.