DMTF1 Antibody – Mouse Monoclonal

This gene encodes a transcription factor that contains a cyclin D-binding domain, three central Myb-like repeats, and two flanking acidic transactivation domains at the N- and C-termini. The encoded protein is induced by the oncogenic Ras signaling pathway and functions as a tumor suppressor by activating the transcription of ARF and thus the ARF-p53 pathway to arrest cell growth or induce apoptosis. It also activates the transcription of aminopeptidase N and may play a role in hematopoietic cell differentiation. The transcriptional activity of this protein is regulated by binding of D-cyclins. This gene is hemizygously deleted in approximately 40% of human non-small-cell lung cancer and is a potential prognostic and gene-therapy target for non-small-cell lung cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Function: Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest

By similarity. Binds to the consensus sequence 5'-CCCG[GT]ATGT-3'

By similarity. Isoform 1 may cooperate with MYB to activate transcription of the ANPEP gene. Isoform 2 may antagonize transcriptional activation by isoform 1. Ref.2

Subunit structure: Interacts with the D-type cyclins CCND1, CCND2 and CCND3

By similarity. Interaction with D-type cyclins may modulate transcriptional activation by this protein

By similarity.

Subcellular location: Nucleus Ref.8.

Tissue specificity: Expressed at relatively low levels in colonic mucosa, ovary, peripheral leukocytes, prostate and small intestine, and at higher levels in spleen, testis and thymus. Expressed in multiple regions of the brain and CNS including amygdala, caudate, corpus callosum, hippocampus, substantia nigra and subthalamic nucleus. Isoform 1 is the predominant isoform in monocytes, macrophages and neutrophils, isoform 2 is most strongly expressed in peripheral blood leukocytes and quiescent CD34 positive cells, and isoform 3 is expressed at low levels in all hematopoietic cell types. Expression is frequently reduced in non-small-cell lung carcinomas (NSCLC) due to hemizygous gene deletion, strongly suggesting that this locus is haploinsufficient for tumor suppression. Loss of this locus frequently occurs in tumors which retain wild-type CDKN2A/ARF and p53/TP53 loci. Hemizygous gene deletion has also been observed in leukemic blasts from patients with abnormalities of the long arm of chromosome 7. Ref.1 Ref.2 Ref.8

Developmental stage: Isoform 2 expression is down-regulated during myeloid differentiation, while the expression of isoform 1 and isoform 3 remain constant.

Post-translational modification: Phosphorylated by the cyclin-D2/CDK4, cyclin-D3/CDK4 and cyclin-D2/CDK6 complexes and to a lesser extent by the cyclin-D1/CDK4 complex

By similarity.

Sequence similarities: Belongs to the DMTF1 family.Contains 1 HTH myb-type DNA-binding domain.Contains 2 Myb-like domains.

Sequence caution: The sequence BAD92467.1 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.