Silkworm is an economically important insect that synthetizes silk proteins for silk production in silk gland, and silk gland cells undergo endoreplication during larval period. Transcription factor Myc is essential for cell growth and proliferation. Although silkworm Myc gene has been identified previously, its biological functions in silkworm silk gland are still largely unknown. In this study, we examined whether enhanced Myc expression in silk gland could facilitate cell growth and silk production. Based on a transgenic approach, Myc was driven by the promoter of the fibroin heavy chain (FibH) gene to be successfully overexpressed in posterior silk gland. Enhanced Myc expression in the PSG elevated FibH expression by about 20% compared to the control, and also increased the weight and shell rate of the cocoon shell. Further investigation confirmed that Myc overexpression increased nucleus size and DNA content of the PSG cells by promoting the transcription of the genes involved in DNA replication. Therefore, we conclude that enhanced Myc expression promotes DNA replication and silk protein expression in endoreplicating silk gland cells, which subsequently raises silk yield.
AbstractTumor suppressor PTEN dephosphorylates signaling lipid PIP3 produced by PI3Ks. Abundant PIP3 promotes cell growth and proliferation. PTEN is the second most highly mutated protein in cancer and is drugless. The detailed mechanism at the membrane of this pivotal phosphatase is unknown hindering understanding and drug discovery. Here for the first time, exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane, its interaction with membranes composed of zwitterionic phosphatidylcholine and anionic phosphatidylserine and phosphatidylinositol, including signaling lipids PIP2 and PIP3, and moving away from the zwitterionic and getting absorbed onto the anionic membrane that harbors the PIP3. PIP3 then allosterically unfolds the N-terminal PIP2 binding domain, translocating it to the membrane where its polybasic motif interacts with PIP2, localizing on microdomains enriched in signaling lipids, as PI3K does. Finally, we determined PTEN catalytic action at the membrane, all in line with available experimental observations.
The three human RAS proteins are mutated and constitutively activated in ∼20% of cancers leading to cell growth and proliferation. For the past three decades, many attempts have been made to inhibit these proteins with little success. Recently; however, multiple methods have emerged to inhibit KRAS, the most prevalently mutated isoform. These methods and the underlying biology will be discussed in this review with a special focus on KRAS-plasma membrane interactions.
Summary / AbstractAminoacyl-tRNA synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNA, but many of them perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl-tRNA synthetase (PheRS/FARS) levels are elevated in various cancer cells compared to their normal cell counterparts. However, whether and how these levels might contribute to tumor formation was not clear. Here, we show that PheRS is required for cell growth and proliferation. Interestingly, elevated expression of the α-PheRS subunit alone stimulates cell growth and proliferation. In the wing discs system, this leads to a strong increase of mitotic cells. Clonal analysis of twin spots in dividing follicle cells revealed that elevated expression of the α-PheRS subunit causes cells to grow and proliferate about 25% faster than their normal twin cells. Importantly, this stimulation of growth and proliferation neither required the β-PheRS subunit nor the aminoacylation activity, and it did not visibly stimulate translation. These results, therefore, revealed a non-canonical function of an ancient housekeeping enzyme, providing novel insight into its roles in health and diseases.
calderon encodes an organic cation transporter of the major facilitator superfamily required for cell growth and proliferation of Drosophila tissues