Abstract
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.
Highlights
More than 20 years ago, Ching et al, initially isolated three novel binding partners of cyclin-dependent kinase 5 (CDK5) activator p35 from rat brain cDNA library by using the yeast two-hybrid screen assay [1]
CDK5RAP3 was initially considered as a putative tumor suppressor since it is found to be markedly reduced in 32% of primary head and neck squamous cell carcinoma (HNSCC), and inhibits cellular transformation and tumor growth in vitro and in vivo [5]
We overview the current research on CDK5RAP3, and highlight the following points
Summary
More than 20 years ago, Ching et al, initially isolated three novel binding partners of cyclin-dependent kinase 5 (CDK5) activator p35 from rat brain cDNA library by using the yeast two-hybrid screen assay [1]. CDK5RAP3 has no well-defined functional domains and described enzymatic activity except a small region of leucine zipper responsible for protein dimerization and two LXXLL motifs governing the linkage with transcription factors [2, 6, 10] (Figure 1B). These features are reminiscent of its interactions with various proteins and its functions as a transcriptional modulator. CDK5RAP3 is observed to combine with the animo-terminal region of ARF, and form a ternary complex with ARF and human double minute 2 (HDM2) in U2OS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
