Protein phosphatase 1 is a key player in nuclear events.
Reversible protein phosphorylation at serine (Ser), threonine (Thr) and tyrosine (Tyr) residues is among the major regulatory mechanism in eukaryotic cells. The eukaryotic genome encodes many protein kinases and protein phosphatases. However, the localization, activity and specificity towards phosphatase substrates are dictated by a large array of phosphatase binding and regulatory subunits. For protein phosphatase 1 (PP1) more than 200 binding subunits have been described. The various PP1 isoforms and the binding subunits can be located throughout the cell, including in the nucleus. It follows that several nuclear specific PP1 binding proteins (PIPs) have been described and these will be discussed. Among them are PNUTS (phosphatase 1 nuclear targeting subunit), NIPP1 (nuclear inhibitor of PP1) and CREB (cAMP-responsive element-binding protein), which have all been associated with transcription. In fact PP1 can associate with transcription factors fulfilling an important regulatory function, in this respect it can bind to Hox11, human factor C1 (HCF1) and myocyte enhancer factor-2 (MEF2). PP1 also regulates cell cycle progression and centrosome maturation and splitting, again by binding to specific regulatory proteins. Moreover, PP1 together with other protein phosphatases control the entry into mitosis by regulating the activity of mitotic kinases. Thus, PP1, its binding proteins and/or the phosphorylation states of both, directly control a vast array of cell nucleus associated functions, many of which are starting to be unraveled.
Laboratório de Neurociências e Sinalização Celular, Centro de Biologia Celular, iBiMED, SACS, Universidade de Aveiro, Portugal. Electronic address: srebelo@ua.pt.
Sandra
S
Rebelo
Laboratório de Neurociências e Sinalização Celular, Centro de Biologia Celular, iBiMED, SACS, Universidade de Aveiro, Portugal.
Mariana
M
Santos
Laboratório de Neurociências e Sinalização Celular, Centro de Biologia Celular, iBiMED, SACS, Universidade de Aveiro, Portugal.
Filipa
F
Martins
Laboratório de Neurociências e Sinalização Celular, Centro de Biologia Celular, iBiMED, SACS, Universidade de Aveiro, Portugal.
Edgar F
EF
da Cruz e Silva
Laboratório de Neurociências e Sinalização Celular, Centro de Biologia Celular, iBiMED, SACS, Universidade de Aveiro, Portugal.
Odete A B
OA
da Cruz e Silva
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D014158:Transcription, Genetic
D054645:Protein Phosphatase 1
Gene transcription and cell cycle; Nuclear functions; Protein Phosphatase 1 binding protein; Regulatory subunit