Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription.

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Abstract Text:

X-L Li,Y Arai,H Harada,Y Shima,H Yoshida,S Rokudai,Y Aikawa,A Kimura,I Kitabayashi,X-L Li,Y Arai,H Harada,Y Shima,H Yoshida,S Rokudai,Y Aikawa,A Kimura,I Kitabayashi,

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.

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Publishing Authors By Initials

XL Li,Y Arai,H Harada,Y Shima,H Yoshida,S Rokudai,Y Aikawa,A Kimura,I Kitabayashi,XL Li,Y Arai,H Harada,Y Shima,H Yoshida,S Rokudai,Y Aikawa,A Kimura,I Kitabayashi,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Oncogene

VOLUME: 26

Page Numbers: 7231-9

Journal Abbreviation:

ISSN: 0950-9232

DAY: 28

MONTH: 05

YEAR: 2007

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription.

AFFILIATION: Molecular Oncology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Oncogene

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription Related Publications

• Chromatin regulation by AML1 complex.
• Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription.
• Phosphorylation of PML is essential for activation of C/EBP epsilon and PU.1 to accelerate granulocytic differentiation.
• Roles of the histone acetyltransferase monocytic leukemia zinc finger protein in normal and malignant hematopoiesis.