Differential Regulation of B-Raf Isoforms by Phosphorylation and AutoinhibitoryMechanisms

Hmitou, Isabelle; Druillennec, Sabine; Valluet, Agathe; Peyssonnaux, Carole; Eychène, Alain

doi:10.1128/mcb.01265-06

Cited by 36 publications

(44 citation statements)

References 57 publications

(110 reference statements)

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“…BRAF has several naturally occurring splice variants in mice and humans that may influence cellular proliferation and resistance to regulation [26,27]. These splice variants may also play a role in early carcinogenesis, with shifts in splicing leading to cells undergoing more rapid proliferation without a mutation.…”

Section: Discussionmentioning

confidence: 98%

Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant

Smith¹,

Salajegheh²,

Weinstein³

et al. 2011

Human Pathology

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Mutation of the BRAF gene is common in thyroid cancer. Follicular variant of papillary thyroid carcinoma is a variant of papillary thyroid carcinoma that has created continuous diagnostic controversies among pathologists. The aims of this study are to (1) investigate whether follicular variant of papillary thyroid carcinoma has a different pattern of BRAF mutation than conventional papillary thyroid carcinoma in a large cohort of patients with typical features of follicular variant of papillary thyroid carcinoma and (2) to study the relationship of clinicopathological features of papillary thyroid carcinomas with BRAF mutation. Tissue blocks from 76 patients with diagnostic features of papillary thyroid carcinomas (40 with conventional type and 36 with follicular variant) were included in the study. From these, DNA was extracted and BRAF V600E mutations were detected by polymerase chain reaction followed by restriction enzyme digestion and sequencing of exon 15. Analysis of the data indicated that BRAF V600E mutation is significantly more common in conventional papillary thyroid carcinoma (58% versus 31%, P = .022). Furthermore, the mutation was often noted in female patients (P = .017), in high-stage cancers (P = .034), and in tumors with mild lymphocytic thyroiditis (P = .006). We concluded that follicular variant of papillary thyroid carcinoma differs from conventional papillary thyroid carcinoma in the rate of BRAF mutation. The results of this study add further information indicating that mutations in BRAF play a role in thyroid cancer development and progression.

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Section: Discussionmentioning

confidence: 98%

Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant

Smith¹,

Salajegheh²,

Weinstein³

et al. 2011

Human Pathology

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“…Immunoprecipitation and western blot analysis were performed as previously described 57 . In brief, lysates of HEK293T or 5-10 embryos were prepared with cold lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis

Pegoraro¹,

Figueiredo²,

Maczkowiak³

et al. 2015

Nat Commun

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How metabolism regulators play roles during early development remains elusive. Here we show that PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4), a glycolysis regulator, is critical for controlling dorsal ectoderm global patterning in gastrulating frog embryos via a non-glycolytic function. PFKFB4 is required for dorsal ectoderm progenitors to proceed towards more specified fates including neural and non-neural ectoderm, neural crest or placodes. This function is mediated by Akt signalling, a major pathway that integrates cell homeostasis and survival parameters. Restoring Akt signalling rescues the loss of PFKFB4 in vivo. In contrast, glycolysis is not essential for frog development at this stage. Our study reveals the existence of a PFKFB4-Akt checkpoint that links cell homeostasis to the ability of progenitor cells to undergo differentiation, and uncovers glycolysis-independent functions of PFKFB4.

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“…HeLa 705 cells [32] were seeded into 96-well plates (5,000 cells/well) and allowed to attach overnight. Particles (100µL), containing 0.1–1 mg/ml protamine and 150 nM of either 705 sequence [3, 22] or anti-B-Raf siRNA sequence (5’-AUGAUCCAGAUCCAAUUCUdTdT-3’), were added to the well in a total volume of 200–300 µL Opti-Mem (Gibco-BRL).…”

Section: Methodsmentioning

confidence: 99%

Characterization and performance of nucleic acid nanoparticles combined with protamine and gold

et al. 2009

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Macromolecular nucleic acids such as DNA vaccines, siRNA, and splice-site switching oligomers (SSO) have vast chemotherapeutic potential. Nanoparticulate biomaterials hold promise for DNA and RNA delivery when a means for binding is identified that retains structure-function and provides stabilization by the nanoparticles. In order to provide these benefits of binding, we combined DNA and RNA with protamine— demonstrating association to gold microparticles by electrophoretic, gel shot, fluorescence, and dynamic laser light spectroscopy (DLLS). A pivotal finding in these studies is that the Au-protamine-DNA conjugates greatly stabilize the DNA; and DNA structure and vaccine activity are maintained even after exposure to physical, chemical, and temperature-accelerated degradation. Specifically, protamine formed nanoparticles when complexed to RNA. These complexes could be detected by gel shift and were probed by high throughput absorbance difference spectroscopy (HTADS). Biological activity of these RNA nanoparticles (RNPs) was demonstrated also by a human tumor cell splice-site switching assay and by siRNA delivery against B-Raf—a key cancer target. Finally, RNA:protamine particles inhibited growth of cultured human tumor cells and bacteria. These data provide new insights into DNA and RNA nanoparticles and prospects for their delivery and chemotherapeutic activity.

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Differential Regulation of B-Raf Isoforms by Phosphorylation and AutoinhibitoryMechanisms

Cited by 36 publications

References 57 publications

Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant

Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant

PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis

Characterization and performance of nucleic acid nanoparticles combined with protamine and gold

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