Publications by authors named "Ching-En Lee"
Adopting a proper topology is crucial for transmembrane proteins to perform their functions. We previously reported that ceramide regulates a transmembrane protein called TM4SF20 (transmembrane 4 L six family member 20) through topological inversion by altering the direction through which the protein is translocated across membranes during translation. This regulatory mechanism, denoted regulated alternative translocation (RAT), depends on a GN motif present in the first transmembrane helix of TM4SF20.
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- TM4SF20 is a membrane protein that normally inhibits the activation of CREB3L1, a factor that regulates cell growth and collagen production.
- Ceramide triggers a change in the orientation of TM4SF20 within the cell membrane, leading to the activation of CREB3L1.
- This process, termed "regulated alternative translocation," allows TM4SF20 to switch positions in the membrane, which is not dependent on TRAM2 when ceramide is present.
CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor and activated through Regulated Intramembrane Proteolysis (RIP), is essential for collagen production by osteoblasts during bone development. Here, we show that TGF-β (transforming growth factor-β), a cytokine known to stimulate production of collagen during wound healing and fibrotic diseases, induces proteolytic activation of CREB3L1 in human A549 cells. This activation results from inhibition of expression of TM4SF20 (transmembrane 4 L6 family member 20), which normally inhibits RIP of CREB3L1.
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- The ability of group A streptococcus (GAS) to sense carbon sources through the virulence regulator Mga, which is affected by phosphorylation from phosphotransferase system (PTS) components, enhances its pathogenicity.
- Phosphorylation of Mga decreases its activity in promoting the transcription of virulence genes like emm, particularly when mutated to mimic phosphorylation; this implies a regulatory mechanism that influences virulence based on available sugars.
- Non-phosphorylated and certain phosphomimetic mutants of Mga showed reduced ability to cause disease in models, highlighting the critical role of PTS-mediated phosphorylation in regulating virulence in GAS and suggesting that similar mechanisms may exist in other Gram-positive pathogens.