The TPTE gene family: cellular expression, subcellular localization and alternative splicing

Tapparel, Caroline; Reymond, Alexandre; Girardet, Christophe; Guillou, Louis; Lyle, Robert; Lamon, Christine; Hutter, Pierre; Antonarakis, Stylianos E.

doi:10.1016/j.gene.2003.09.038

Cited by 84 publications

(71 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The same cloning strategy was used to create the expression vectors encoding the RcsB-CpxR chimeras. The GFP-CpxR chimeras were created by ligation of an NcoI-EcoRI fragment of the CMV-59 EGFP Painbeni et al (1993) expression vector (Tapparel et al, 2003) with EcoRI-NcoI fragments of pBAD-CpxR 100, 117 and 134. All constructs were verified by sequencing using appropriate primers.…”

Section: Methodsmentioning

confidence: 99%

The DNA-binding domain of the Escherichia coli CpxR two-component response regulator is constitutively active and cannot be fully attenuated by fused adjacent heterologous regulatory domains

2006

Self Cite

View full text Add to dashboard Cite

Two-component systems (TCS) based on a sensor histidine kinase and a phosphorylated cognate target regulator allow rapid responses to environmental changes. TCS are highly evolutionarily conserved, though in only a few cases are the inducing signals understood. This study focuses on the Escherichia coli CpxR response regulator that responds to periplasmic and outer-membrane stress. N-terminal deletion mutations have been isolated that render the transcription factor constitutively active, indicating that the N terminus functions, in part, to keep the C-terminal winged-helix DNA-binding effector domain in an inactive state. Analysis of truncations spanning the CpxR interdomain region revealed that mutants retaining the alpha5 helix significantly augment activation. Hybrid proteins obtained by fusing the CpxR effector domain to structurally similar heterologous N-terminal regulatory domains, or even GFP, failed to restore repression to the C-terminal domain. These findings shed light on the mechanism of CpxR effector domain activation and on the investigation of constitutive mutants obtained by truncation in other TCS

show abstract

Section: Methodsmentioning

confidence: 99%

The DNA-binding domain of the Escherichia coli CpxR two-component response regulator is constitutively active and cannot be fully attenuated by fused adjacent heterologous regulatory domains

2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, the mammalian PTEN-related proteins TPTE and TPIP also show high conservation in this region (Figure 1b). The fact that TPTE and TPIP differ from PTEN in the presence of a large N-terminal extension responsible of the localization of these proteins at non-nuclear intracellular compartments, 14,15 suggests that the NLS-like region is essential for the biological activity of these PTEN-related phosphatases. In support of this are the findings that the N-terminal region of PTEN possesses a functional phosphatydilinositol-4,5-biphosphate (PIP2) binding motif, which overlaps with key residues defined in the PTEN NLS-like domain (see Figure 1a).…”

Section: Molecular Mechanisms Of Pten Nuclear Accumulationmentioning

confidence: 99%

Nuclear PTEN: a tale of many tails

Gil

Andrés-Pons²,

Pulido³

2006

Cell Death Differ

View full text Add to dashboard Cite

The PTEN tumour suppressor is one of the more commonly inactivated proteins in human cancer and a key regulator of the PI3K/Akt survival pathway. Its direct involvement in human disease, as well as its important role in many cellular processes, including cell development and differentiation, cell growth, apoptosis, cell motility, cell size, stem cell survival, and longevity, has made PTEN the focus of attention of many researchers and clinicians. The major biological function of PTEN resides in its phosphatase activity towards the lipid second messenger phosphatydilinositol-3,4,5-triphosphate (PIP3), antagonizing the activity of the PI3K oncoproteins, and the association of PTEN to lipids at the plasma membrane is required to exert this function. [1][2][3] In addition, the presence of PTEN in the nucleus of many different cell types, and the finding of unexpected PTEN functions in the nucleus has revealed that the regulation of its nuclear/cytoplasmic distribution may also be a key mechanism to drive PTEN functions.4-6 Here, we discuss the current models to explain the regulation of PTEN nuclear accumulation, and the molecular linkage between the targeting of PTEN to the nucleus and to lipid membranes. The distinct pathways that mediate nuclear PTEN functions in the control of cell growth and apoptosis are also discussed. Molecular Mechanisms of PTEN Nuclear AccumulationThe tumour suppressor PTEN protein is present in the nucleus of different cell types, including cell lines and tissue cells.7-10 However, PTEN amino-acid sequence lacks obvious canonical nuclear localization signal sequences (NLS) or nuclear export sequences (NES) that could account for the targeting of the protein in or out of the nucleus, making elusive the molecular basis of PTEN nuclear/cytoplasmic distribution. Recent findings, however, suggest that PTEN entry and accumulation in the nucleus may be controlled by a variety of mechanisms. Chung et al.11 have reported that, in the MCF-7 breast carcinoma cell line, PTEN may be transported into the nucleus using several putative NLS-like sequences located in the PTP and the C2 domains of the protein. Mutating such NLS-like sequences individually did not affect PTEN nuclear/ cytoplasmic distribution. However, combined mutations of the NLS-like sequences caused defective PTEN nuclear accumulation. Based on the differential interaction of the major vault protein (MVP) with wild-type PTEN and with the NLS-like mutants, as well as on the nuclear localization pattern of MVP, the authors propose a model of PTEN nuclear import mediated by MVP. Interestingly, PTEN was found in this study to interact with importin a and b proteins, although such interaction was also observed in the NLS-like mutants that displayed defective nuclear accumulation. A second model of PTEN nuclear entry has been proposed by Liu et al.12 Using PTEN fusion proteins of variable size, the authors of this study noticed that large PTEN fusion proteins (4100 kDa) did not show nuclear localization, whereas PTEN alone (47 kDa) or a GFP-P...

show abstract

“…TPTE encodes a PTEN-related tyrosine phosphatase, is 99-fold down-regulated, and plays an important role in suppressing signaling via tyrosine-phosphorylated proteins (42). MGC15419 is 20-fold down-regulated and may be critical for the controlled degradation of cellular regulatory proteins (43).…”

Section: Ptcl-nos Tumor Profile Signaturementioning

confidence: 99%

“…TPTE is a 100-fold down-regulated PTEN-related tyrosine phosphatase that, if active, would switch off tyrosine kinase -driven oncogenic pathways (42). SUI1/MOF2 is 25-fold down-regulated and functions as a modulator of accuracy at both initiation and elongation phases of translation (60).…”

Section: Ptcl-nos Tumor Profile Signaturementioning

confidence: 99%

Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures

Mahadevan

Spier²,

Croce

et al. 2005

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct ''tumor profile signatures'' for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, a-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.

show abstract

The TPTE gene family: cellular expression, subcellular localization and alternative splicing

Cited by 84 publications

References 28 publications

The DNA-binding domain of the Escherichia coli CpxR two-component response regulator is constitutively active and cannot be fully attenuated by fused adjacent heterologous regulatory domains

The DNA-binding domain of the Escherichia coli CpxR two-component response regulator is constitutively active and cannot be fully attenuated by fused adjacent heterologous regulatory domains

Nuclear PTEN: a tale of many tails

Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures

Contact Info

Product

Resources

About