Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The AML1 transcription factor complex is the most frequent target of leukemia-associated chromosomal translocations.
Homeodomain-interacting protein kinase 2
(
HIPK2
) is a part of the AML1 complex and activates AML1-mediated transcription. However, chromosomal translocations and mutations of
HIPK2
have not been reported. In the current study, we screened mutations of the
HIPK2
gene in 50 cases of acute myeloid leukemia (AML) and in 80 cases of
myelodysplastic syndrome
(
MDS
). Results indicated there were two missense mutations (R868W and N958I) in the speckle-retention signal (SRS) domain of
HIPK2
. Subcellular localization analyses indicated that the two mutants were largely localized to nuclear regions with conical or ring shapes, and were somewhat diffused in the nucleus, in contrast to the wild type, which were mainly localized in nuclear speckles. The mutations impaired the overlapping localization of AML1 and
HIPK2
. The mutants showed decreased activities and a dominant-negative function over wild-type protein in AML1- and p53-dependent transcription. These findings suggest that dysfunction of
HIPK2
may play a role in the pathogenesis of leukemia.
...
PMID:Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. 1753 75
