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)
Interferon regulatory factor 1
(
IRF-1
) is a transcriptional activator in the interferon system and acts as a tumor suppressor. The structurally related IRF-2 represses the effects of
IRF-1
by competitive binding to the same DNA sequence elements. Changes in the relative balance between
IRF-1
and IRF-2 lead to dysregulation of cell growth and may play a role in the development of neoplasias. The loss of functional
IRF-1
has been observed in a number of patients with
myelodysplastic syndrome
(
MDS
) and leukemia, suggesting a potentially critical role of
IRF-1
in leukemogenesis. We studied the expression of both transcription factors in peripheral blood (PB) and bone marrow (BM) cells of children with juvenile myelomonocytic leukemia (JMML) using RT-PCR and Southern blot hybridization. No significant difference between the expression levels of
IRF-1
and IRF-2 could be detected in PB and BM of patients with JMML and normal donors. Although our results are preliminary they suggest that neither the tumor suppressor gene
IRF-1
nor the oncogene IRF-2 is involved in the pathogenesis of JMML.
...
PMID:Expression of interferon regulatory factor 1 and 2 in hematopoietic cells of children with juvenile myelomonocytic leukemia. 1060 88
Interferon regulatory factor 1
(
IRF-1
) plays a vital role in cell proliferation and cell differentiation by acting as a tumor suppressor gene and its role is linked to various types of cancers, including leukemia and pre-leukemia
myelodysplasia
. Mutations in the coding region of the
IRF-1
are likely to influence the
IRF-1
and its DNA binding affinity. The molecular mechanism of the DNA recognition with the
IRF-1
protein upon mutations is still unknown. In this study, we have elucidated the structural and functional behavior of the wild-type and mutant (K75E and E222K)
IRF-1
proteins and their corresponding molecular mechanisms with DNA recognition at the molecular level, using molecular dynamics simulations. Furthermore, we also applied the docking approach to examine the binding between the
IRF-1
protein and DNA upon mutations. This study evidently explains that, due to mutations, the
IRF-1
structure loses its stability and becomes more flexible than the wild-type protein. This structural loss might affect
IRF-1
-DNA interaction and lead to the inhibition of cancer suppression. Identifying the effects of
IRF-1
at the molecular level will be beneficial for designing drugs for
IRF-1
associated cancers. These drugs should be designed so that they can help reactivate the
IRF-1
function, by increasing the transcriptional activity, to treat leukemia.
...
PMID:Effect of novel leukemia mutations (K75E & E222K) on interferon regulatory factor 1 and its interaction with DNA: insights from molecular dynamics simulations and docking studies. 3261 31
