RUNX1 is an eukaryotic gene and the protein encoded by this gene is a transcription factor associated with M2 AML, a type of leukemia. It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα). RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex.
Function
RUNX1 is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Two transcript variants encoding different isoforms have been found for this gene. [cite web | title = Entrez Gene: RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=861| accessdate = ] The consensus binding site for CBF has been identified to be a 7 bp sequence PyGPyGGTPy. Py denotes pyrimidine which can be either cytosine or thymine.[cite journal | author = Melnikova IN, Crute BE, Wang S, Speck NA | title = Sequence specificity of the core-binding factor | journal = J. Virol. | volume = 67 | issue = 4 | pages = 2408–11 | year = 1993 | month = April | pmid = 8445737 | pmc = 240414 | doi = | url = http://jvi.asm.org/cgi/content/abstract/67/4/2408 | issn = ] ] Mouse knockout
Mice embryos with homozygous mutations on RUNX1 died at about 12.5 days. The embryos displayed lack of fetal liver hematopoiesis.[cite journal | author = Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR | title = AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis | journal = Cell | volume = 84 | issue = 2 | pages = 321–30 | year = 1996 | month = January | pmid = 8565077 | doi = 10.1016/S0092-8674(00)80986-1 | url = | issn = ] ]Similar experiments from a different research group demonstrated that the knockout embryos die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS).[cite journal | author = Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA | title = Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 8 | pages = 3444–9 | year = 1996 | month = April | pmid = 8622955 | pmc = 39628 | doi = | url = http://www.pnas.org/content/93/8/3444.abstract]
issn = ] ee also
* Core binding factor
* RUNX2
* RUNX3
References
Further reading
PBB_Further_reading
citations =
*cite journal | author=Nucifora G, Rowley JD |title=AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. |journal=Blood |volume=86 |issue= 1 |pages= 1–14 |year= 1995 |pmid= 7795214 |doi=
*cite journal | author=Perry C, Eldor A, Soreq H |title=Runx1/AML1 in leukemia: disrupted association with diverse protein partners. |journal=Leuk. Res. |volume=26 |issue= 3 |pages= 221–8 |year= 2002 |pmid= 11792409 |doi=
*cite journal | author=Imai O, Kurokawa M, Izutsu K, "et al." |title=Mutational analyses of the AML1 gene in patients with myelodysplastic syndrome. |journal=Leuk. Lymphoma |volume=43 |issue= 3 |pages= 617–21 |year= 2003 |pmid= 12002768 |doi=
*cite journal | author=Hart SM, Foroni L |title=Core binding factor genes and human leukemia. |journal=Haematologica |volume=87 |issue= 12 |pages= 1307–23 |year= 2003 |pmid= 12495904 |doi=
*cite journal | author=Asou N |title=The role of a Runt domain transcription factor AML1/RUNX1 in leukemogenesis and its clinical implications. |journal=Crit. Rev. Oncol. Hematol. |volume=45 |issue= 2 |pages= 129–50 |year= 2003 |pmid= 12604126 |doi=
*cite journal | author=Michaud J, Scott HS, Escher R |title=AML1 interconnected pathways of leukemogenesis. |journal=Cancer Invest. |volume=21 |issue= 1 |pages= 105–36 |year= 2003 |pmid= 12643014 |doi=
*cite journal | author=Ganly P, Walker LC, Morris CM |title=Familial mutations of the transcription factor RUNX1 (AML1, CBFA2) predispose to acute myeloid leukemia. |journal=Leuk. Lymphoma |volume=45 |issue= 1 |pages= 1–10 |year= 2004 |pmid= 15061191 |doi=
*cite journal | author=Yamada R, Tokuhiro S, Chang X, Yamamoto K |title=SLC22A4 and RUNX1: identification of RA susceptible genes. |journal=J. Mol. Med. |volume=82 |issue= 9 |pages= 558–64 |year= 2005 |pmid= 15184985 |doi= 10.1007/s00109-004-0547-y
*cite journal | author=Harada H, Harada Y, Kimura A |title=Implications of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome (MDS): future molecular therapeutic directions for MDS. |journal=Current cancer drug targets |volume=6 |issue= 6 |pages= 553–65 |year= 2006 |pmid= 17017876 |doi=
External links
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