Nuclear and subnuclear targeting sequences of the protein phosphatase-1 regulator NIPP1

Jagiello, Izabela; Eynde, Aleyde Van; Vulsteke, Veerle; Beullens, Monique; Boudrez, An; Keppens, Stefaan; Stalmans, Willy; Bollen, Mathieu

doi:10.1242/jcs.113.21.3761

Cited by 47 publications

(1 citation statement)

References 21 publications

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“…NIPP1-GFP and GFP-SDS22 plasmids were described before (Jagiello et al, 2000;Lesage et al, 2007). For GFP-I3 expression, the human I3 cDNA was cloned from the image clone 40029469 into a pEGFP-C1 vector.…”

Section: Plasmids and Constructsmentioning

confidence: 99%

Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore‐bound protein phosphatase‐1

et al. 2014

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Faithful chromosome segregation during mitosis is tightly regulated by opposing activities of Aurora B kinase and protein phosphatase-1 (PP1). PP1 function at kinetochores has been linked to SDS22, but the exact localization of SDS22 and how it affects PP1 are controversial. Here, we confirm that SDS22 is required for PP1 activity, but show that SDS22 does not normally localize to kinetochores. Instead, SDS22 is kept in solution by formation of a ternary complex with PP1 and inhibitor-3 (I3). Depletion of I3 does not affect the amount of PP1 at kinetochores but causes quantitative association of SDS22 with PP1 on KNL1 at the kinetochore. Such accumulation of SDS22 at kinetochores interferes with PP1 activity and inhibits Aurora B threonine-232 dephosphorylation, which leads to increased Aurora B activity in metaphase and persistence in anaphase accompanied with segregation defects. We propose a model in which I3 regulates an SDS22-mediated PP1 activation step in solution that precedes SDS22 dissociation and transfer of PP1 to kinetochores, and which is required for PP1 to efficiently antagonize Aurora B.

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Section: Plasmids and Constructsmentioning

confidence: 99%

Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore‐bound protein phosphatase‐1

et al. 2014

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Myosin16b: The COOH‐tail region directs localization to the nucleus and overexpression delays S‐phase progression

Cameron

Liu

Mixon

et al. 2006

Cell Motil. Cytoskeleton

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Rat Myo16a and Myo16b comprise the founding members of class XVI myosin and are characterized by an N-terminal ankyrin repeat domain thought to mediate an association with protein phosphatase 1 catalytic subunits 1alpha and 1gamma. Myo16b is the principal isoform and reveals predominant expression in developing neural tissue. Here, we use COS-7 cells as a model system to develop an understanding of Myo16b function. We find that Myo16b displays predominant localization in the nucleus of cells transitioning through interphase, but is not associated with processes of mitosis. Using a panel of EGFP-Myo16b-expression plasmids in transient transfection studies, we identified the COOH-terminal residues 1616-1912 as necessary and solely sufficient to target Myo16b to the nucleus. We show that the Myo16b-tail region directs localization to a nuclear compartment containing profilin and polymerized actin, which appears to form a three-dimensional meshwork through the depth of the nucleus. Further, we demonstrate that this compartment localizes within euchromatic regions of the genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both markers of S-phase of the cell cycle. Cells transiently expressing Myo16b or Myo16b-tail region show limited incorporation of BrdU, delayed progression through S-phase of the cell cycle, and curtailed cellular proliferation.

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Regulation of protein phosphatase 1γ activity in hypoxia through increased interaction with NIPP1: Implications for cellular metabolism

Comerford

Leonard

Cummins

et al. 2006

Journal Cellular Physiology

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Eukaryotic cells sense decreased oxygen levels and respond by altering their metabolic strategy to sustain non-respiratory ATP production through glycolysis, and thus promote cell survival in a hypoxic environment. Protein phosphatase 1 (PP1) has been recently implicated in the governance of the rational use of energy when metabolic substrates are abundant and contributes to cellular recovery following metabolic stress. Under conditions of hypoxia, the expression of the gamma isoform of PP1 (PP1gamma), is diminished, an event we have hypothesized to be involved in the adaptive cellular response to hypoxia. Decreased PP1gamma activity in hypoxia has a profound impact on the activity of the cAMP response element binding protein (CREB), a major transcriptional regulator of metabolic genes and processes. Here, we demonstrate a further mechanism leading to inhibition of PP1 activity in hypoxia which occurs at least in part through increased association with the nuclear inhibitor of PP1 (NIPP1), an event dependent upon decreased basal cAMP/PKA-dependent signaling. Using a dominant negative NIPP1 construct, we provide evidence that NIPP1 plays a major role in the regulation of both CREB protein expression and CREB-dependent transcription in hypoxia. Furthermore, we demonstrate functional sequellae of such events including altered gene expression and recovery of cellular ATP levels. In summary, we demonstrate that interaction with NIPP1 mediates decreased PP1gamma activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia.

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Nuclear and subnuclear targeting sequences of the protein phosphatase-1 regulator NIPP1

Cited by 47 publications

References 21 publications

Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore‐bound protein phosphatase‐1

Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore‐bound protein phosphatase‐1

Myosin16b: The COOH‐tail region directs localization to the nucleus and overexpression delays S‐phase progression

Regulation of protein phosphatase 1γ activity in hypoxia through increased interaction with NIPP1: Implications for cellular metabolism

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