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The p38 MAPK Pathway in Prostate Cancer

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Prostate Cancer

Part of the book series: Protein Reviews ((PRON,volume 16))

Abstract

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.

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  1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC, 20057, USA

    Daniel Djakiew B.Sc, Ph.D.

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Correspondence to Daniel Djakiew B.Sc, Ph.D. .

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  1. , Depts of Urology, and, Mayo Clinic College of Medicine, 200 1st Street SW., Rochester, 55905, Minnesota, USA

    Donald J. Tindall

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Djakiew, D. (2013). The p38 MAPK Pathway in Prostate Cancer. In: Tindall, D. (eds) Prostate Cancer. Protein Reviews, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6828-8_8

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