scholarly journals Cyclin-Dependent Kinase 5 Regulatory Subunit Associated Protein 3: Potential Functions and Implications for Development and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Linna Sheng ◽  
Jiaxuan Li ◽  
Shengfang Rao ◽  
Zhijun Yang ◽  
Yonghong Huang

Cyclin-dependent kinase 5 (CDK5) regulatory subunit associated protein 3 (CDK5RAP3, also named as C53 or LZAP) was initially identified as a binding protein of CDK5 activator p35. To date, CDK5RAP3 has been reported to interact with a range of proteins involved in cellular events ranging from cell cycle, apoptosis, and invasion to UFMylation modification and endoplasmic reticulum stress. Owing to its crucial roles in cellular processes, CDK5RAP3 is demonstrated to be not only an active participant in embryonic and mammalian tissue development, but also a key regulator in the onset and progress of human cancers such as head and neck squamous cell carcinoma, gastric cancer, hepatocellular cancer, lung cancer, kidney cancer and breast cancer. Notwithstanding, the detailed function of CDK5RAP3 and its mechanism remain poorly defined. Here, we briefly described a history of the discovery of CDK5RAP3, and systematically overviewed its gene structural and distribution features. We also focused on the known functions of this protein and its implications for embryogenesis and tissue development, as well as diseases especially carcinoma. This review may facilitate to understand the molecular and functional basis of CDK5RAP3 and its association with development and disease, and provide a reasonable idea for novel therapeutic opportunities targeting CDK5RAP3.

Genomics ◽  
1996 ◽  
Vol 35 (2) ◽  
pp. 372-375 ◽  
Author(s):  
Toshio Ohshima ◽  
Christine A. Kozak ◽  
James W. Nagle ◽  
Harish C. Pant ◽  
Roscoe O. Brady ◽  
...  

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 88 ◽  
Author(s):  
Rabih Roufayel ◽  
Nimer Murshid

The atypical cyclin-dependent kinase 5 (CDK5) is considered as a neuron-specific kinase that plays important roles in many cellular functions including cell motility and survival. The activation of CDK5 is dependent on interaction with its activator p35, p39, or p25. These activators share a CDK5-binding domain and form a tertiary structure similar to that of cyclins. Upon activation, CDK5/p35 complexes localize primarily in the plasma membrane, cytosol, and perinuclear region. Although other CDKs are activated by cyclins, binding of cyclin D and E showed no effect on CDK5 activation. However, it has been shown that CDK5 can be activated by cyclin I, which results in anti-apoptotic functions due to the increased expression of Bcl-2 family proteins. Treatment with the CDK5 inhibitor roscovitine sensitizes cells to heat-induced apoptosis and its phosphorylation, which results in prevention of the apoptotic protein functions. Here, we highlight the regulatory mechanisms of CDK5 and its roles in cellular processes such as gene regulation, cell survival, and apoptosis.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chengcheng Liu ◽  
Xiaoyan Zhai ◽  
Bin Zhao ◽  
Yanfei Wang ◽  
Zhigang Xu

Abstract In contrast to conventional cyclin-dependent kinases that are important for mitotic cell division, cyclin-dependent kinase 5 (CDK5) is predominantly activated in post-mitotic cells and is involved in various cellular events. The kinase activity of CDK5 is tightly regulated by specific activators including p35, p39, and cyclin I (CCNI). Here we show that cyclin I-like (CCNI2), a homolog of CCNI, interacts with CDK5 and activates the kinase activity of CDK5. Different from CCNI, which colocalizes with CDK5 in the nuclei in transfected cells, CCNI2 mainly retains CDK5 in the cytoplasm as well as on the cell membrane. Furthermore, although the expression level of CCNI2 mRNA and CCNI2 protein do not change significantly during cell cycle, depletion of CCNI2 with siRNA affects cell cycle progression as well as cell proliferation. In conclusion, our data strongly suggest that CCNI2 is a novel CDK5 activator and is involved in cell cycle regulation.


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