The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.
Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.
The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.
Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.
Schumanniophyton problematicum is a species of plant in the family Rubiaceae. It is found in Ivory Coast, Ghana, and Sierra Leone. It is threatened by habitat loss.
Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.
Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.
Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.
Factor interacting with PAPOLA and CPSF1 is a protein that in humans is encoded by the FIP1L1 gene. A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal hypereosinophilia and leukemic diseases in humans.
Bromodomain-containing protein 4 is a protein that in humans is encoded by the BRD4 gene.
General transcription factor IIF subunit 1 is a protein that in humans is encoded by the GTF2F1 gene.
Cyclin-K is a protein that in humans is encoded by the CCNK gene.
In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.
Volasertib is an experimental small molecule inhibitor of the PLK1 protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. Volasertib is the second in a novel class of drugs called dihydropteridinone derivatives.
A flavonoid alkaloid also known as a flavoalkaloid is a type of natural product produced by plants that contains both a flavonoid core structure and a nitrogen containing substituent so that the substance is also classified as an alkaloid. The most common flavonoid alkaloids contain a nitrogen heterocycle such as a pyridine or piperidine which is covalently bonded to the A-ring of a chromone. One flavonoid alkaloid, lilaline, was isolated from Lilium candidum in 1987. The synthesis of flavonoid alkaloids has been achieved
Zotiraciclib (TG02) is a potent oral spectrum selective kinase inhibitor for the treatment of cancer. It was discovered in Singapore by S*BIO Pte Ltd and falls under the category of small molecule macrocycles. It crosses the blood brain barrier and acts by depleting Myc through the inhibition of cyclin-dependent kinase 9 (CDK9). It is one of a number of CDK inhibitors under investigation; others targeting CDK9 for the treatment of acute myeloid leukemia include alvocidib and atuveciclib. Myc overexpression is a known factor in many cancers, with 80 percent of glioblastomas characterized by this property. Zotiraciclib has been granted orphan drug designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of gliomas.
