CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth

• Authors: Hongchen Yan, Nanjing Agricultural University; Jun-Jie Xu, Nanjing Agricultural University; Ilyas Ali, Nanjing Agricultural University; Wei Zhang, Nanjing Agricultural University; Ming Jiang, Huazhong University of Science & Technology; Guiping Li, Huazhong University of Science & Technology; Yong Teng, Emory University; Guangxun Zhu, Huazhong University of Science & Technology; Yafei Cai, Nanjing Agricultural University
• Journal Title: CELL PROLIFERATION
• Volume: Volume 55, Number 5
• Publisher: WILEY | 2022-05-04, Pages e13240-e13240
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1111/cpr.13240
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology; ACTIVATOR-BINDING-PROTEIN; BOUND RIBOSOMES; LZAP; PROMOTES; PROLIFERATION; TRANSLOCATION; PROGNOSIS; MECHANISM; CARCINOMA; AUTOPHAGY

Abstract

Purpose and Materials: CDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis. Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death. Results: CDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth. CDK5RAP3 deficiency partly blocks the cell cycle in G2/M by downregulating CDK1 (Cyclin-dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p-mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth. Conclusions: Our experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.