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Nowak, Jonathan A.; Malowitz, Jonathan; Girgenrath, Mahasweta; Kostek, Christine A.; Kravetz, Amanda J.; Dominov, Janice A.; Miller, Jeffrey B.

doi:10.1186/1471-2121-5-1

Cited by 22 publications

(3 citation statements)

References 46 publications

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“…These actions are, at least in part, mediated through transcriptional repression of the INK4A-ARF locus, encoding cell cycle inhibitors p16 ink4a and p19 arf [13] , and p21 waf1/cip1 [19] . Interestingly it has been reported that loss of p16 ink4a induces spontaneous immortalization of myogenic cells [20] and satellite cells can be conditionally immortalized by constitutive expression of Bmi1 and telomerase [21] . It is therefore possible that Bmi1 plays a crucial role in maintaining the proliferative potential of satellite cells, possibly through its actions on p16 ink4a and p19 arf .…”

Section: Introductionmentioning

confidence: 99%

Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

Robson

Foggia

Radunović³

et al. 2011

PLoS ONE

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Satellite cells are the resident stem cell population of the adult mammalian skeletal muscle and they play a crucial role in its homeostasis and in its regenerative capacity after injury. We show here that the Polycomb group (PcG) gene Bmi1 is expressed in both the Pax7 positive (+)/Myf5 negative (−) stem cell population as well as the Pax7+/Myf5+ committed myogenic progenitor population. Depletion of Pax7+/Myf5− satellite cells with reciprocal increase in Pax7+/Myf5+ as well as MyoD positive (+) cells is seen in Bmi1−/− mice leading to reduced postnatal muscle fiber size and impaired regeneration upon injury. Bmi1−/− satellite cells have a reduced proliferative capacity and fail to re-enter the cell cycle when stimulated by high serum conditions in vitro, in keeping with a cell intrinsic defect. Thus, both the in vivo and in vitro results suggest that Bmi1 plays a crucial role in the maintenance of the stem cell pool in postnatal skeletal muscle and is essential for efficient muscle regeneration after injury especially after repeated muscle injury.

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Section: Introductionmentioning

confidence: 99%

Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

Robson

Foggia

Radunović³

et al. 2011

PLoS ONE

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“…The MEF lines were grown in Ham's F-10 medium (Gibco) supplemented with 10% fetal bovine serum (Gibco). Authentication included ATCC certification, immunoblotting ( Nowak et al, 2004 ), and testing to confirm that double knockout Bax-/-;Bak-/- MEFs, but not single knockouts or wild type, were resistant to killing by etoposide ( Fig. 6 F) ( Ke et al, 2018 ; Wei et al, 2001 ).…”

Section: Methodsmentioning

confidence: 99%

Downstream events initiated by expression of FSHD-associated DUX4: Studies of nucleocytoplasmic transport, γH2AX accumulation, and Bax/Bak-dependence

et al. 2022

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Abnormal expression in skeletal muscle of the double homeobox transcription factor DUX4 underlies pathogenesis in facioscapulohumeral muscular dystrophy (FSHD). Though multiple changes are known to be initiated by aberrant DUX4 expression, the downstream events initiated by DUX4 remain incompletely understood. In this study, we examined plausible downstream events initiated by DUX4. First, we found that nucleocytoplasmic protein export appeared to be decreased upon DUX4 expression as indicated by nuclear accumulation of a shuttle-GFP reporter. Second, building on studies from other labs, we showed that phospho(Ser139)-H2AX (γH2AX), an indicator of double-strand DNA breaks, accumulated both in human FSHD1 myotube nuclei upon endogenous DUX4 expression and in Bax-/-;Bak-/- (double knockout), SV40-immortalized mouse embryonic fibroblasts upon exogenous DUX4 expression. In contrast, DUX4-induced caspase 3/7 activation was prevented in Bax-/-;Bak-/- double knockout SV40-MEFs, but not by single knockouts of Bax, Bak, or Bid. Thus, aberrant DUX4 expression appeared to alter nucleocytoplasmic protein transport and generate double-strand DNA breaks in FSHD1 myotube nuclei, and the Bax/Bak pathway is required for DUX4-induced caspase activation but not γH2AX accumulation. These results add to our knowledge of downstream events induced by aberrant DUX4 expression and suggest possibilities for further mechanistic investigation.

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“…The reactive site (designated P1 position) in the inhibitory loop is determinant and controls much of the inhibitory activity towards the specific targeted protease. It has been proven that the presence of either Lysine or Arginine at the P1 position obstructs any protease from cleaving adjacently to those residues in the protein substrate, while the Asn13, Tyr17 and Tyr18 stabilize the canonical loop in the reactive site [ 47 ]. These features are central to the biological activity of the protein and permit the orientation of its functional moieties [ 48 ].…”

Section: Protease Inhibitors and Schistosomiasismentioning

confidence: 99%

Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

2021

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Proteins hardly function in isolation; they form complexes with other proteins or molecules to mediate cell signaling and control cellular processes in various organisms. Protein interactions control mechanisms that lead to normal and/or disease states. The use of competitive small molecule inhibitors to disrupt disease-relevant protein–protein interactions (PPIs) holds great promise for the development of new drugs. Schistosome invasion of the human host involves a variety of cross-species protein interactions. The pathogen expresses specific proteins that not only facilitate the breach of physical and biochemical barriers present in skin, but also evade the immune system and digestion of human hemoglobin, allowing for survival in the host for years. However, only a small number of specific protein interactions between the host and parasite have been functionally characterized; thus, in-depth understanding of the molecular mechanisms of these interactions is a key component in the development of new treatment methods. Efforts are now focused on developing a schistosomiasis vaccine, as a proposed better strategy used either alone or in combination with Praziquantel to control and eliminate this disease. This review will highlight protein interactions in schistosomes that can be targeted by specific PPI inhibitors for the design of an alternative treatment to Praziquantel.

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Untitled

Cited by 22 publications

References 46 publications

Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

Downstream events initiated by expression of FSHD-associated DUX4: Studies of nucleocytoplasmic transport, γH2AX accumulation, and Bax/Bak-dependence

Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

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