Disease relevance of PyK

• Furthermore, transfection assays with a rat hepatoma cell line and Drosophila Schneider cells revealed that reactive oxygen intermediates dramatically decrease the transcriptional activities of the Sp1-dependent aldolase A and pyruvate kinase M2 promoters leading to reduced reporter gene expression [1].

High impact information on PyK

• This sequence is also capable of directing less efficient nuclear transport of a normally cytoplasmic protein, pyruvate kinase [2].
• Sp family members and nuclear factor-Y cooperatively stimulate transcription from the rat pyruvate kinase M gene distal promoter region via their direct interactions [3].
• The three distal transcriptional regulatory elements of the rat pyruvate kinase M gene, referred to as boxes A, B, and C, are located around -270 base pairs upstream from the transcriptional initiation site [3].
• The analog was also found to be a substrate for all of the enzymes tested, including creatine kinase, pyruvate kinase, hexokinase, and myosin, with values of Km and Vmax that were within a factor of 10 of those for ATP [4].
• Site-directed mutagenesis of cis-regulatory elements in the 5' flanking region of the rat pyruvate kinase M gene revealed that two out of the three GC boxes (-133/-124 and -48/-39) are involved in the stimulation of a core promoter (-35/+46) [5].

Biological context of PyK

• A small segment of chromosome 1, 12AB-12C, in Drosophila melanogaster is dosage-sensitive for the glycolytic enzyme pyruvate kinase (EC 2.7.1.40) [6].
• Deletion mapping was applied to identify the promoter region and cis-acting elements 5' of PyK [7].
• Additionally, PyK might share a regulatory region with an unknown neighboring gene [7].
• The results revealed that the regions -1475 approximately -1033 and -1033 approximately -534 of the 5' end of PyK possessed positive regulatory function for Pyk expression; i.e., increased gene expression [7].
• No TATA box or downstream promoter element were identified around the transcription start site of Pyk [7].

Anatomical context of PyK

• Changes in the activity of 3 enzymes--lactate dehydrogenase (LDH), soluble malate dehydrogenase (sMDH), and pyruvate kinase (PK)--in homogenates of larval salivary glands of Drosophila melanogaster were studied before and after the induction of heat sensitive puffs with trinactin [8].

Analytical, diagnostic and therapeutic context of PyK

• However, the results of the developmental profile of Pyk expression by Northern blot analysis suggested that the effects of ecdysone on Pyk were repressive, not inductive [7].
• Southern blot analysis, PCR, and sequencing were used to determine the content of a Drosophila pyruvate kinase (Pyk) genomic clone, lambdaPK61 [7].

References