Extracellular signals regulate P19 cell proliferation and differentiation through ERK kinase phosphatization Lin28.

On February 8th the international academic journal Journal of Biochemistry published online the latest findings of the Gao Daming Research Group of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, entitled Extracellular-Signaled Kinases (ERKs) Phosphorylate Lin28a Protein to Modulate P19 Cell Proliferation and Evolution.
the proliferation and differentiation of stem cells are two closely related processes, both of which are regulated by extracell signals.
, mapK-ERK signaling paths play a key role in controlling cell proliferation and differentiation.
-ERK signal can make cells more likely to pass through the early G1 stage of the cell cycle, and if the MAPK signal continues to active, it often induces stem cell differentiation, which in turn can link proliferation to differentiation.
Lin28a, a highly conservative RNA binding protein, was first reported in 1984 as a cryptosomal worm and was involved in cell proliferation and cell multi-potential regulation.
Lin28a functions mainly by binding to the pregenitors of the let-7 family miRNA, which further affects the expression of the downstream target gene of let-7, and the genes known to be regulated include c-Myc, Ras, cyclin D1, and Lin28a itself.
Under the guidance of researcher Gao Daming, Ph.D. student Liu Xiangyuan identified the key phosphorylation modification bit Ser200 of Lin28a by immuno-precipitation-mass spectrometry, and found that Erk1/2 mediated Ser200 bits of phosphorylation.
, using CRISPR/Cas9 technology, the researchers introduced a point mutation in the coding position of the lin28a gene Ser200 in P19 teratoma stem cells, resulting in Lin28a Ser200Ala (missing phosphate) and Ser200Asp (phosphate simulation) being knocked into the cell line.
Ser200Ala knocks into the cell line faster and differentiates more slowly during RA induction than wild P19 cells and Ser200Asp knock-in cell line.
the Ser200Asp knocks into the cell line at the slowest rate of proliferation and ra induces the fastest differentiation.
ERK mediated the phosphateization of Lin28a's Ser200 bits, lowered cyclinD1 by way of let-7 dependence, and regulated the proliferation and differentiation of P19 cells.
further experiments found that Lin28a was phosphorylated, the ability to inhibit the maturity of let-7 weakened, so that the target gene cyclinD1 downstream of let-7 was lowered, P19 EC cell proliferation slowed down and began to differentiate.
study revealed the important regulatory role of Lin28a post-translation modification on Lin28a function and deepened the understanding of the molecular mechanism of stem cell proliferation and differentiation.
the research has been greatly assisted by researchers Wu Ligang, Chen Lingling and Zhou Hu, researchers of Shanghai Pharmaceutical Research Institute, and has been supported by research funds from the National Natural Science Foundation of China and the Ministry of Science and Technology.
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