Global Medical Discovery features paper: Different Effects of p52SHC1 and p52SHC3 on the Cell Cycle of Neurons and Neural Stem Cells

Significance Statement

Many studies clearly demonstrate the important roles of SHC1 and SHC3 in neuronal functions. However, the exact functional differences between SHC1 and SHC3, especially on the aspect of their isoforms, have not been revealed in primary neurons or neuronal precursor cells. In this study, we used

RNA interference to knock down the expression of p52SHC1and p52SHC3 in purified primary cortical neurons and neural stem cells, respectively. We also used adenovirus to overexpress p52SHC1 in primary neurons and p52SHC3 in neural stem cells to confirm their roles in neural cell cycle.

In the present study, p52SHC1 RNAi  resulted in significantly fewer percentage of G2-M phase cells in primary neural stem cells along with down-regulated cyclin A and cyclin E proteins. However, the exogenous expression of SHC1 in purified primary cortical neurons in this study did not seem to change the cell cycle distribution, although cyclin A, CDK2 and p-CDK2 were all up-regulated.

In Ning Tang and colleagues study, knockdown of p52SHC3 expression by RNAi significantly affected the cell cycle distribution and the expression levels of many cell cycle regulators. Specifically, RNAi of p52SHC3 decreased the percentage of G0/G1 phase neurons but increased the percentages of S phase and G2/M phase neurons, The changed cell cycle distribution may be caused by the changed levels of the following proteins: the upregulation of cyclin D1 which may cause reduction in the percentage of G0/G1 phase neurons; the up-regulation of cyclin E and CDK2 which may push cells to pass the G1/S boundary to enter S phase; and the up-regulation of cyclin A and CDK2 which may lead to the cells to enter G2/M phase. All these results clearly indicated that some of the neurons had reentered the cell cycle after p52SHC3 RNAi. Overexpression of exogenous p52SHC3 in neural stem cells increased the percentage of G0-G1 phase cells and decreased the percentage of G2-M phase cells by downregulating the protein levels of cyclin A, cyclin D1, and cyclin E, demonstrating a CDK2-independent cell cycle arrest.

Ning Tang and colleagues deminstrated that p52SHC1 plays an essential role in regulating cellular proliferation and p52SHC3 has crucial function in maintaining the mitotic quiescence of neurons. Controlling these domain-mediated signals could be a target in determining the fate of neural cells in the cell cycle.   

 

About The Author

Dr. Ning Tang received his Bachelor Degree in biology science from Shandong University, China, in 2003. He received his Ph. D from Institute of Basic Medical Sciences, Academy of Military Medical Sciences in 2010, majored in cell biology.

Currently, he works in Reproductive Medicine Center of Jinan Military General Hospital as an embryologist, Jinan, China. 

About The Author

Dr. Dan Lyu received her Bachelor Degree in 2005, from Chengdu Sport University, Chengdu, China. In 2008, she received her Master Degree from Hebei Medical University, Shijiazhuang, China and in 2011, she received her Ph,D from Capital Medical University, Beijing, China, majored in pain medicine.

She is now a clinical doctor in Tianjin First Central Hospital, Tianjin, China. Her research focuses on pain related neural pathological and physiological alteration. 

 

Reference

Tang N^1,2, Lyu D^1,3, Liu T¹, Chen F¹, Jing S¹, Hao T², Liu S¹. Different Effects of p52SHC1 and p52SHC3 on the Cell Cycle of Neurons and Neural Stem Cells. J Cell Physiol. 2016 ;231(1):172-80. doi: 10.1002/jcp.25069.

Show Affiliations

1 State Key Laboratory of Proteomics and, Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, P. R. China.

2 Reproductive Medicine Center, Jinan Military General Hospital, Jinan, P. R. China.

3 Dan Lyu is currently working in Department of Pain Management, Tianjin First Center Hospital, Tianjin, P. R. China.  

 

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