Abstract
Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5–p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.
Highlights
Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family
To clarify the regulatory role of CDK5 and p35 in male reproduction and understand the relationship between CDK5 and prostate cancer, we demonstrated that human chorionic gonadotrophin, which is involved in major reproductive processes, regulates CDK5–p35 activity in rodent Leydig cells [25]
We reported that CDK5 promotes the proliferation of prostate cancer cells through a direct protein–protein interaction with signal transducer and activator of transcription 3 (STAT3) protein
Summary
Cyclin-dependent kinase 5 (CDK5) is an essential member of the proline-directed serine/threonine kinase family [1]. The CDK5–p35 complex has essential roles in the regulation of central nervous system (CNS) development [2,7] and neurodegenerative diseases [8,9]. Our previous study demonstrated that the CDK5–p35 complex could be regulated by nerve growth factor signaling in neuronal differentiation, and the cAMP-related pathway plays an alternative role in this regulation [10]. CDK5 is important for the regulation of dendrite development in the primary culture of rat neurons [16]. Our previous study demonstrated the essential role of CDK5 under Abl regulation using a Drosophila neurodegenerative model [18]. The blocking of CDK5–p25 interaction decreased CDK5 activation, and notably, reduced tau protein phosphorylation and accumulation, which is an important factor in the neuropathology of AD [19]
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