The EGF-like Homeotic Protein dlk Affects Cell Growth and Interacts with Growth-Modulating Molecules in the Yeast Two-Hybrid System

Baladrón, Victoriano; Ruiz-Hidalgo, Marı́a José; Bonvini, Ezio; Gubina, Elena; Notario, Vicente; Laborda, Jorge

doi:10.1006/bbrc.2002.6431

Cited by 49 publications

(43 citation statements)

References 53 publications

(66 reference statements)

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“…In response to glucocorticoids, Balb/c 3T3 cells had diminished levels of DLK1 and grew faster (Baladron et al, 2002). In addition, Gaetano et al (1992) found that the neuroblastoma cell line SMS-KCNR, cultured with dibutyryl cyclic AMP (dbcAMP), had a markedly increased expression of DLK1 associated with a transition to a more mature chromaffin phenotype with no change in the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

DLK1: increased expression in gliomas and associated with oncogenic activities

et al. 2006

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DLK1 (delta-like) is a transmembrane and secreted protein in the epidermal growth factor-like homeotic family. Although expressed widely during embryonic development, only a few tissues retain the expression in adults. Neuroendocrine tumors often highly express this protein; therefore, we hypothesized that brain tumors might also express it. This study found that the expression of DLK1 in gliomas was higher than that in normal brain (Po0.05). After stable transfection of a DLK1 cDNA expression vector into GBM cell lines, their proliferation was increased. Furthermore, they lost contact inhibition, had enhanced anchorage-independent growth in soft agar, and had significantly greater capacity to migrate. Western blot studies showed that expression of cyclin D1, CDK2, and E2F4 were increased, and Rb levels were decreased in these cells. DLK1 was found on the cell surface and secreted in the medium from the transfected GBM cells. DLK1-enriched condition medium stimulated the growth of glioblastoma multiforme cell lines and explants. DLK1 antibody blocked cell growth stimulated by DLK1. In summary, these results suggest that DLK1 may play a role in the formation or progression of gliomas.

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Section: Discussionmentioning

confidence: 99%

DLK1: increased expression in gliomas and associated with oncogenic activities

et al. 2006

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“…In both cases PGRN binds its partner weakly, with affinities in the micromolar range, (94,95) and associates with the target protein through an EGF-containing module. PGRN reportedly binds the membrane protein Dlk, (96) which is also rich in EGF modules, and although not yet tested, an affinity for EGF modules may prove a recurrent pattern in PGRN-protein interactions. Interactions of PGRN with intracellular proteins such as cyclin T have been reported, although their physiological significance is uncertain.…”

Section: Progranulin Interaction With Other Proteinsmentioning

confidence: 98%

The granulin gene family: from cancer to dementia

2009

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The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine-rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN.

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“…For all experiments, C2C12 cells were seeded at 10,000 cells/cm 2 and cultured for 48 hours before further treatment. For transfection experiments, cells were equilibrated in serum-free medium for 1 hour prior to transfection for 4 hours with 1 µg/12-well pCD2-Dlk1FL (containing full-length mouse Dlk1 cDNA (Baladrón et al, 2002) or control pCD2 vector using the Lipofectamine 2000 protocol (Life Technologies, Denmark). Immediately following transfection, cells were induced to differentiate in DMEM + 2% horse serum + 1% PS for 5 days.…”

Section: Overexpression Of Dlk1 In the Myogenic Cell Line C2c12mentioning

confidence: 99%

Dual role of delta-like 1 homolog (DLK1) in skeletal muscle development and adult muscle regeneration

et al. 2013

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SUMMARYMuscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential myogenic inducers remain poorly described. Here, we show that delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability to inhibit adipogenesis, is a crucial regulator of the myogenic program in skeletal muscle. Dlk1 −/− mice were developmentally retarded in their muscle mass and function owing to inhibition of the myogenic program during embryogenesis. Surprisingly however, Dlk1 depletion improves in vitro and in vivo adult skeletal muscle regeneration by substantial enhancement of the myogenic program and muscle function, possibly by means of an increased number of available myogenic precursor cells. By contrast, Dlk1 fails to alter the adipogenic commitment of muscle-derived progenitors in vitro, as well as intramuscular fat deposition during in vivo regeneration. Collectively, our results suggest a novel and surprising dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration.

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The EGF-like Homeotic Protein dlk Affects Cell Growth and Interacts with Growth-Modulating Molecules in the Yeast Two-Hybrid System

Cited by 49 publications

References 53 publications

DLK1: increased expression in gliomas and associated with oncogenic activities

DLK1: increased expression in gliomas and associated with oncogenic activities

The granulin gene family: from cancer to dementia

Dual role of delta-like 1 homolog (DLK1) in skeletal muscle development and adult muscle regeneration

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