Tumor suppression and potentiation by manipulation of pp32 expression

Bai, Jining; Brody, Jonathan R.; Kadkol, Shrihari S.; Pasternack, Gary R.

doi:10.1038/sj.onc.1204294

Cited by 69 publications

(60 citation statements)

References 20 publications

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“…The greatest difference in favor of IGF-II was observed for acidic nuclear phosphoprotein 32 (ANP32) gene (40). ANP32 is a protein involved in embryogenesis that is switched off in differentiated cells.…”

Section: Differential Transcriptional Effects Of Insulin and Igf-ii 4mentioning

confidence: 99%

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Pandini

Medico

Conte

et al. 2003

Journal of Biological Chemistry

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The human insulin receptor (IR) exists in two isoforms (IR-A and IR-B). IR-A is a short isoform, generated by the skipping of exon 11, a small exon encoding for 12 amino acid residues at the carboxyl terminus of the IR ␣-subunit. Recently, we found that IR-A is the predominant isoform in fetal tissues and malignant cells and binds with a high affinity not only insulin but also insulin-like growth factor-II (IGF-II). To investigate whether the activation of IR-A by the two ligands differentially activate post-receptor molecular mechanisms, we studied gene expression in response to IR-A activation by either insulin or IGF-II, using microarray technology. To avoid the interfering effect of the IGF-IR, IGF-II binding to the IR-A was studied in IGF-IR-deficient murine fibroblasts (R ؊ cells) transfected with the human IR-A cDNA (R؊ /IR-A cells). Gene expression was studied at 0.5, 3, and 8 h. We found that 214 transcripts were similarly regulated by insulin and IGF-II, whereas 45 genes were differentially transcribed. Eighteen of these differentially regulated genes were responsive to only one of the two ligands (12 to insulin and 6 to IGF-II). Twenty-seven transcripts were regulated by both insulin and IGF-II, but a significant difference between the two ligands was present at least in one time point. Interestingly, IGF-II was a more potent and/or persistent regulator than insulin for these genes. Results were validated by measuring the expression of 12 genes by quantitative real-time reverse transcriptase-PCR. In conclusion, we show that insulin and IGF-II, acting via the same receptor, may differentially affect gene expression in cells. These studies provide a molecular basis for understanding some of the biological differences between the two ligands and may help to clarify the biological role of IR-A in embryonic/fetal growth and the selective biological advantage that malignant cells producing IGF-II may acquire via IR-A overexpression.

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Section: Differential Transcriptional Effects Of Insulin and Igf-ii 4mentioning

confidence: 99%

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Pandini

Medico

Conte

et al. 2003

Journal of Biological Chemistry

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“…It has been shown that PHAPI can combat Ras and Myc-induced oncogenic transformation and that its highly acidic COOH terminus is necessary for this function (37,38). In addition, PHAPI has been implicated as an inhibitor of protein phosphatase 2A, a modulator of interactions between microtubules and associated proteins, and a regulator of histone acetylation (39)(40)(41).…”

Section: Pp2amentioning

confidence: 99%

Enhanced Sensitivity to Cytochrome c–Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells

et al. 2006

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“…LANP is also abundant in selfrenewing stem cell-like populations and cell subtypes known for their rapid proliferative ability, such as intestinal crypt epithelial cells and prostatic epithelial cells competent for cell renewal (19,39). There is also some evidence to suggest that LANP and its family members regulate the proliferation of tumor cells (2,6,(13)(14)(15). Incidentally, the SET gene was originally identified as a putative oncogene, identified as the locus for a translocation breakpoint event in acute undifferentiated leukemia, although the cellular basis for oncogenesis is far from clear.…”

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confidence: 99%

Generation and Characterization of LANP/pp32 Null Mice

Opal

Garcı́a

McCall

et al. 2004

Molecular and Cellular Biology

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The leucine-rich acidic nuclear protein (LANP) belongs to a family of evolutionarily conserved proteins that are characterized by an amino-terminal domain rich in leucine residues followed by a carboxy-terminal acidic tail. LANP has been implicated in the regulation of a variety of cellular processes including RNA transport, transcription, apoptosis, vesicular trafficking, and intracellular signaling. Abundantly expressed in the developing cerebellum, this protein has also been hypothesized to play a role in cerebellar morphogenesis. LANP has been implicated in disease biology as well, both as a mediator of toxicity in spinocerebellar ataxia type 1 and as a tumor suppressor in cancers of the breast and prostate. To better understand the function of this multifaceted protein, we have generated mice lacking LANP. Surprisingly, these mice are viable and fertile. In addition we could not discern any derangements in any of the major organ systems, including the nervous system, which we have studied in detail. Overall our results point to a functional redundancy of LANP's function, most likely provided by its closely related family members.Leucine-rich acidic nuclear protein (LANP or pp32 [for phosphoprotein with a molecular mass of 32 kDa]) is a member of the leucine-rich family of proteins (16-18). These proteins are involved in a variety of pathways including signaling, protein degradation, cytoskeletal dynamics, and morphogenesis, presumably based on the ability of the leucine-rich repeat (LRR) domains to serve as adapter sites for protein-protein interactions.For LANP, the hydrophobic LRRs reside in its N-terminal domain, giving LANP a globular head domain. The C-terminal domain, on the other hand, is extended and hydrophilic, engaging interactors by virtue of its ionic interactions (23,27,30,31).Several proteins have extensive homology to LANP, both in displaying LRRs in their N terminal domains and in demonstrating extended acidic tail domains. These proteins represent true LANP family members that have probably arisen by gene duplication. The nomenclature of LANP family members is confusing because the same protein has been given more than one name based on the context of isolation. Thus APRIL, an acronym derived from A protein rich in leucines, is also known as PAL-31, for proliferation-associated leucine-rich protein, MW 31kDa, and SSP-29, for silver-stainable protein with a molecular mass of 29 kDa (24,25,41). CPD1 (cerebellar postnatal development protein 1), another LANP family member, has been called LANP-like protein (LANP-L) (21, 28). Two human homologues of LANP/pp32 have been called pp32r1 and pp32r2 to signify that they are related (14,15). Besides having homology with these proteins, LANP family members also have limited homology to template-activating factor (TAF) proteins, TAF-1 alpha and beta (the latter being the product of the SET oncogene). The TAF-1 proteins, like the LANP family members, demonstrate long acidic C-terminal domains but, unlike LANP, do not display LRRs in their Nterminal doma...

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Tumor suppression and potentiation by manipulation of pp32 expression

Cited by 69 publications

References 20 publications

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Enhanced Sensitivity to Cytochrome c–Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells

Generation and Characterization of LANP/pp32 Null Mice

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