The CD44 Proteins in Embryonic Development and in Cancer

Sherman, Larry S.; Sleeman, Jonathan P.; Dall, P.; Hekele, Armin; Moll, Jürgen; Ponta, Helmut; Herrlich, Peter

doi:10.1007/978-3-642-61107-0_15

Cited by 50 publications

(53 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Variant CD44v6 has been shown to promote metastasis formation independent of interactions with hyaluronic acid (Sleeman et al, 1996). In the case of melanoma the in¯uence of variant CD44v6 expression on the metastatic potential of the cells seems to be rather low (Simon et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid

et al. 2001

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid

et al. 2001

View full text Add to dashboard Cite

“…of Pathology, Nijmegen, The Netherlands); MAT-Lu and AT-2.1, rat prostate carcinoma (Isaacs et al, 1986); AR42J and ARIP, rat pancreas carcinoma (ATCC); RG2, rat glioblastoma (ATCC); BDX2, rat ®brosarcoma (Sleeman et al, 1996); and MT-450, rat breast adenocarcinoma (Kim, 1986;Sleeman et al, 1999).…”

Section: Cell Linesmentioning

confidence: 99%

Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis

et al. 2002

View full text Add to dashboard Cite

Hyperforin is a plant derived antibiotic from St. John's wort. Here we describe a novel activity of hyperforin, namely its ability to inhibit the growth of tumour cells by induction of apoptosis. Hyperforin inhibited the growth of various human and rat tumour cell lines in vivo, with IC 50 values between 3 ± 15 mM. Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-speci®c morphological changes. In MT-450 mammary carcinoma cells hyperforin increased the activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was blocked by the broad-range caspase inhibitor zVAD.fmk. When added to MT-450 cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial transmembrane potential Dc m , and subsequent morphological changes such as homogenization and vacuolization of mitochondria. Monitoring of Dc m revealed that the hyperforin-mediated mitochondrial permeability transition can not be prevented by zVAD.fmk. This indicates that mitochondrial permeabilization is a cause rather than a consequence of caspase activation. Moreover, hyperforin was capable of releasing cytochrome c from isolated mitochondria. These ®ndings suggest that hyperforin activates a mitochondria-mediated apoptosis pathway. In vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel, without any signs of acute toxicity. Owing to the combination of signi®cant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration.

show abstract

“…In particular, alternative splicing of CD44 impacts embryonic development and immune response (15)(16)(17)(18). Up to 10 variant exon sequences can be included in the mature CD44 mRNA.…”

mentioning

confidence: 99%

“…Up to 10 variant exon sequences can be included in the mature CD44 mRNA. Among them, variable exon 5 (exon v5) inclusion is associated with tumor progression and T-cell activation (17,19). Sam68 is a target for phosphorylation by extracellular-signal-regulated kinase (ERK), which promotes inclusion of CD44 exon v5 in response to Ras activation by phorbol ester stimulation.…”

mentioning

confidence: 99%

Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain

Meyer

Tripsianes

Vincendeau

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sam68 (Src-associated during mitosis, 68 kDa) is a prototypical member of the STAR (signal transducer and activator of RNA) family of RNA-binding proteins. STAR proteins bind mRNA targets and modulate cellular processes such as cell cycle regulation and tissue development in response to extracellular signals. Sam68 has been shown to modulate alternative splicing of the pre-mRNAs of CD44 and Bcl-xL, which are linked to tumor progression and apoptosis. Sam68 and other STAR proteins recognize bipartite RNA sequences and are thought to function as homodimers. However, the structural and functional roles of the self-association are not known. Here, we present the solution structure of the Sam68 Qua1 homodimerization domain. Each monomer consists of two antiparallel ␣-helices connected by a short loop. The two subunits are arranged perpendicular to each other in an unusual four-helix topology. Mutational analysis of Sam68 in vitro and in a cell-based assay revealed that the Qua1 domain and residues within the dimerization interface are essential for alternative splicing of a CD44 minigene. Together, our results indicate that the Qua1 homodimerization domain is required for regulation of alternative splicing by Sam68. Sam682 (Src-associated during mitosis, 68 kDa) (1) belongs to the STAR (signal transducer and activator of RNA) family of RNAbinding proteins, which also includes Qk1 (quaking 1), SF1 (splicing factor 1), and Gld-1 (germline development defective-1) (2). STAR family proteins link signaling pathways and many aspects of RNA metabolism (splicing, localization, and translation). They are regulated by post-translational modifications such as phosphorylation, acetylation, and arginine methylation (2).Sam68 acts in post-transcriptional regulation of pre-mRNA splicing in response to extracellular signals (3). It is involved in a variety of pathways, including insulin and T-cell receptor signaling (4), and plays a key role in cell cycle regulation (5). Sam68 exhibits binding specificity for homopolymeric poly(U) RNA and has been shown to recognize UAAA or UUUA sequences with high affinity as determined by Systematic Evolution of Ligands by EXponential Enrichment (SELEX) and in vivo crosslinking (6, 7). Post-translational modifications can regulate Sam68 function by critically affecting the accessibility to RNA (8, 9). Tyrosine phosphorylation by Src kinase during mitosis enhances the interaction of Sam68 with Ras-GAP (10) but prevents its association with RNA. On the other hand, acetylation of lysine residues by histone acetyltransferases enhances RNA binding (11). Finally, overexpression of Sam68 has been linked to prostate cancer, cell proliferation, and survival (12).Sam68 has been identified as a key determinant in the alternative splicing of various important RNA targets, like CD44 (13) and Bcl-x L (14), which are linked to apoptosis and cancer. In particular, alternative splicing of CD44 impacts embryonic development and immune response (15-18). Up to 10 variant exon sequences can be included in the mature C...

show abstract

The CD44 Proteins in Embryonic Development and in Cancer

Cited by 50 publications

References 85 publications

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid

Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis

Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain

Contact Info

Product

Resources

About