The p38 MAPK Pathway in Prostate Cancer

  • Daniel Djakiew
Part of the Protein Reviews book series (PRON, volume 16)


The conventional signal transduction pathway for p38 MAPK is complex and diverse. A plethora of signals such as growth factors interact with death receptors to initiate a biochemical cascade by recruitment of activator molecules that in combination activate MAP3Ks. Many drugs intercede at the level of signal, activator, or MAP3Ks to mimic initiation of the signal transduction cascade. In the prostate, these signaling moieties, which include NSAIDs, converge at the level of MAP2Ks, ostensibly MKK6, which phosphorylates up to 4 isoforms of p38 MAPK. Phosphatases such as MKP1 or compounds such as biochanin A are able to antagonize activation of p38 MAPK. Phosphorylation of p38 MAPK allows phosphorylation of MK2 and MK3 that in turn promote stability of the p75NTR transcript. Concurrently, translocation of HuR from the nucleus to the cytoplasm and increased levels of HuR and eIF4E also promote p75NTR mRNA stability and increased levels of the p75NTR protein. In the prostate, the p75NTR functions as both a tumor and metastasis suppressor. In this context, increased expression of p75NTR modulates cell cycle effectors producing cytostasis in G0/G1, as well as mitochondrial effectors that modulate a caspase cascade leading to apoptosis. In addition, increased expression of p75NTR modulates motility effectors, ostensibly NAG-1, that retards cell migration. Hence, activation of the p38 MAPK pathway through a plethora of signal initiating events, leads to tumor and metastasis suppressor activity in prostate cancer cells.


Prostate Cancer Cell Inhibit Cell Migration Reduce Cell Migration p75NTR Expression Initiate Signal Transduction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Mayo Clinic 2013

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular & Cellular BiologyGeorgetown University Medical CenterWashington, DCUSA

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