Phosphoprotein phosphatase 1-interacting proteins as therapeutic targets in prostate cancer

Abstract

Prostate cancer is a major public health concern worldwide, being one of the most prevalent cancers in men. Great improvements have been made both in terms of early diagnosis and therapeutics. However, there is still an urgent need for reliable biomarkers that could overcome the lack of cancer-specificity of prostate-specific antigen, as well as alternative therapeutic targets for advanced metastatic cases. Reversible phosphorylation of proteins is a post-translational modification critical to the regulation of numerous cellular processes. Phosphoprotein phosphatase 1 (PPP1) is a major serine/threonine phosphatase, whose specificity is determined by its interacting proteins. These interactors can be PPP1 substrates, regulators, or even both. Deregulation of this protein-protein interaction network alters cell dynamics and underlies the development of several cancer hallmarks. Therefore, the identification of PPP1 interactome in specific cellular context is of crucial importance. The knowledge on PPP1 complexes in prostate cancer remains scarce, with only 4 holoenzymes characterized in human prostate cancer models. However, an increasing number of PPP1 interactors have been identified as expressed in human prostate tissue, including the tumor suppressors TP53 and RB1. Efforts should be made in order to identify the role of such proteins in prostate carcinogenesis, since only 26 have yet well-recognized roles. Here, we revise literature and human protein databases to provide an in-depth knowledge on the biological significance of PPP1 complexes in human prostate carcinogenesis and their potential use as therapeutic targets for the development of new therapies for prostate cancer.

Keywords: Prostate cancer; Reversible phosphorylation; Phosphoprotein phosphatase 1; Phosphoprotein phosphatase 1-interacting proteins; Protein complexes; Therapeutic targets

Core tip: Protein kinases and phosphatases are challenging and valuable therapeutic targets for cancer. Here, we revise the relevance of phosphoprotein phosphatase 1 and its interactors for prostate carcinogenesis. Although only 4 complexes are characterized in human prostate cancer models, 81 additional interactors are expressed in human prostate tissue and, at least, 29 of which are involved in prostate carcinogenesis. This complex network has promising roles in the development of new therapies for prostate cancer. Therefore, efforts should be made in order to characterize their biological significance in prostate carcinogenesis.