Up-regulation of nuclear PP1alpha and PP1delta in hepatoma cells.

Imai, Yoko; Kakinoki, Yasutaka; Takizawa, Norio; Nakamura, K; Shima, Hiroshi; Kikuchi, Kunimi

doi:10.3892/ijo.14.1.121

Cited by 12 publications

(11 citation statements)

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“…While upregulation of PP1 fosters G1/S transition through the cell cycle [41], it is also known to prevent disassembly of epidermal hemidesmosomes by inhibiting Src family kinases. PP1 achieves this effect without disrupting proliferative signals through the epidermal growth factor receptor [42].…”

Section: Discussionmentioning

confidence: 99%

Microarray profiles of human basal cell carcinoma: Insights into tumor growth and behavior

Howell

Solish

Lü

et al. 2005

Journal of Dermatological Science

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Section: Discussionmentioning

confidence: 99%

Microarray profiles of human basal cell carcinoma: Insights into tumor growth and behavior

Howell

Solish

Lü

et al. 2005

Journal of Dermatological Science

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“…In contrast, PP1a also dephosphorylates the breast and ovarian tumor suppressor protein BRCA1 and may have an oncogenic effect since phosphorylated BRCA1 is considered to be the active form. It has also been reported that overexpression and/or increase in PP1 activity is associated with accelerated growth of malignant cells (Saadat et al, 1995;Imai et al, 1999). Whether PP1a is a tumor suppressor gene or an oncogene remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Protein phosphatase 1a also interacts with Bcl-2, which targets PP1a to dephosphorylate Bad, and may play a role in regulating apoptosis (Ayllon et al, 2001). It has been reported that PP1a is upregulated and PP1 activity is significantly higher in preneoplastic lesions of the liver as well as in hepatomas, suggesting that PP1a may be involved in hepatocarcinogenesis (Saadat et al, 1995;Imai et al, 1999). Another isoform of PP1, PP1g1 is overexpressed and may be involved in accelerated growth of breast cancer cells (Sogawa et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Gene amplification and overexpression of protein phosphatase 1α in oral squamous cell carcinoma cell lines

et al. 2006

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“…In terms of function, protein phosphatase activity must be tightly regulated as the ability of analogues to inhibit PP1 and PP2A have been correlated with anti-cancer activity in human cancer cell lines (60,167). Increased PP1 stability, expression, and nuclear localization has been reported in different cancers (181): oral squamous cell carcinoma cells (75), human hepatomas cells (79,92), and rat hepatomas cells (79,165). There are far less phosphatases in comparison to kinases for the same regulatory phosphorylation mechanisms.…”

Section: Nap1 Phosphorylation and Centrosomal Abnormalitiesmentioning

confidence: 99%

HTLV-1 Tax Effects on Cellular Mitotic Regulation

Merling¹

2007

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The human T-cell leukemia virus 1 (HTLV-1) encodes the tax gene (transactivator encoded by the pX region) which is a potent activator of viral transcription and Nuclear , this cyclin-dependent kinase inhibitor may also play a role in tax-IRS.As part of the research presented in this dissertation, a collection of HTLV-1 tax point mutants were isolated that permit normal growth of S. cerevisiae. Similar to wild-type tax, many mutants (C23W, A108T, L159F, and L235F) transactivated both the HTLV long terminal repeat (LTR) and the NF-!B reporters. The V19M mutant preferentially activated NF-!B, but was attenuated in LTR activation. None of the mutants significantly elevated the levels of p21 CIP1/WAF1 and p27 KIP1 , indicating that dramatic Tax-induced surges in p21and p27 KIP1 occurs by mechanisms distinct from NF-!B and LTR activation. Importantly, the ability of these mutants to activate APC was attenuated or abrogated. These data show that Tax-induced rapid senescence is causally associated with APC activation and suggest iv that the mitotic abnormalities that are associated with premature APC activation might play an important role in cell transformation by Tax.In a parallel study, we demonstrate that Tax interacts with both centrosomal Nek2-associated protein 1 (C-Nap1), a large coiled-coil protein that maintains centrosome cohesion, and protein phosphatase 1 (PP1) and that these interactions localize to the centrosome. Furthermore, in cells expressing tax, C-Nap1 phosphorylation is greatly diminished. C-Nap1 phosphorylation status plays an important role in centrosome cycle progression; PP1-mediated dephosphorylation of C-Nap1 maintains centriolar cohesion during interphase, and never in mitosis A (NIMA)-related kinase 2 (Nek2A)-mediated phosphorylation of C-Nap1 during G2/M triggers C-Nap1 dissociation from duplicated centrosomes permitting normal centrosome disjunction. Our data suggest that Tax, through recruitment of PP1 to C-Nap1, may permit prolonged C-Nap1 dephosphorylation thereby disrupting normal centrosome disjunction leading to observed Tax-induced centrosome abnormalities and distinct microtubule organizing center (MTOC) loss.Our studies have revealed two distinct pathways through which Tax could contribute to oncogenesis. First, our Tax mutants that retained LTR and NF-!B activation properties but were impaired in APC activation were also defective in the ability to transform Rat1 fibroblasts. Therefore, premature APC activation by Tax appears to correlate with the ability of Tax to induce cellular transformation. Second, our demonstration of Tax-mediated alterations in C-Nap1 phosphorylation cycle offers an explanation for the centrosome abnormalities and mitotic apparatus defects observed in response to Tax expression.Chromosomal abnormalities resulting from such mitotic apparatus defects may be expected to contribute to the oncogenic potential of Tax.v

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Up-regulation of nuclear PP1alpha and PP1delta in hepatoma cells.

Cited by 12 publications

References 0 publications

Microarray profiles of human basal cell carcinoma: Insights into tumor growth and behavior

Microarray profiles of human basal cell carcinoma: Insights into tumor growth and behavior

Gene amplification and overexpression of protein phosphatase 1α in oral squamous cell carcinoma cell lines

HTLV-1 Tax Effects on Cellular Mitotic Regulation

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