Disease relevance of PKMYT1

• Inhibition of PKMYT1 expression by the use of specific short interfering RNAs significantly lowered the TPA-induced KSHV lytic cycle of infection [1].
• In this study we defined the function of Myt1 by overexpression studies in both S. pombe and a human osteosarcoma cell line [2].

High impact information on PKMYT1

• Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition [3].
• Here we show that in oocytes from the starfish Asterina pectinifera, the kinase Akt (or protein kinase B (PKB)) phosphorylates and downregulates Myt1, a member of the Wee1 family [3].
• The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase [4].
• Cell-cycle studies indicated that TSAP6 could augment Myt1 activity [4].
• Here we report that overproduction of either kinase-active or kinase-inactive forms of Myt1 blocked the nuclear-cytoplasmic shuttling of cyclin B1 and caused cells to delay in the G2 phase of the cell cycle [5].

Biological context of PKMYT1

• In this study, we have examined the substrate specificity and cell cycle regulation of the human Myt1 kinase [6].
• These findings suggest that human Myt1 is negatively regulated by an M phase-activated kinase and that Myt1 inhibits mitosis due to its specificity for Cdc2.cyclin complexes [6].
• Phosphorylation of these sites is controlled by the opposing activities of the Wee1/Myt1 kinases and the Cdc25 phosphatase [7].
• The decreased level of the Tyr15-phosphorylated form of Cdk1 in virus-infected fibroblasts is due in part to the down-regulation of the expression and activity of the Cdk1 inhibitory kinases Myt1 and Wee1 [8].

Anatomical context of PKMYT1

• The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex [9].
• The addition of 10(-8) to 10(-6) M 1,25[OH]2VD3 to cultured normal human keratinocytes enhanced the expression of Myt1 mRNA preceding Wee1 mRNA; 10(-6) M 1,25[OH]2VD3 unregulated Myt1 mRNA from 6 h to 24 h and Wee1 mRNA from 12 to 48 h [10].

Associations of PKMYT1 with chemical compounds

• The observed suppression of AhR transcriptional activity by colchicine and nocodazole can be associated with G2/M cell cycle arrest in HepG2 cells, as demonstrated by Myt1 protein hyperphosphorylation and FACS analysis [11].

Enzymatic interactions of PKMYT1

• These results suggest that Plk1 phosphorylates Myt1 during M phase [12].

Other interactions of PKMYT1

• In addition, cells overproducing mutant forms of Myt1 lacking the interaction domain exhibited normal trafficking of cyclin B1 and unperturbed cell cycle progression [5].
• The COOH-terminal 63 amino acids of Myt1 were identified as a Cdc2-cyclin B1 interaction domain [5].
• Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate [12].

Analytical, diagnostic and therapeutic context of PKMYT1

• Western blot analysis of the G(2)/M regulatory proteins suggests that cdc2 is involved in the cell cycle block by Myt1 phosphorylation following 2-ME treatment [13].

References