Evidence for an alternate model of human P-glycoprotein structure and biogenesis.

Skach, William R.; Calayag, M C; Lingappa, Vishwanath R.

doi:10.1016/s0021-9258(18)53125-2

Cited by 131 publications

(26 citation statements)

References 26 publications

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“…The mechanism by which EPM is translocated to the outside of the plasma membrane is not known, although cell surface localization of other membrane-associated molecules lacking signal peptides has been reported (Wen et al, 1992;Skach et al, 1993;Ostapchuk et al, 1994;Guo et al, 1998). In such cases, the membrane topology depends on the three-dimensional conformation of the NH 2 -terminal sequence (Denzer et al, 1995;Spiess, 1995;Wahlberg and Spiess, 1997).…”

Section: Epm Is a Member Of The Syntaxin Familymentioning

confidence: 99%

Epimorphin Mediates Mammary Luminal Morphogenesis through Control of C/EBPβ

Hirai

Radisky

Boudreau

et al. 2001

The Journal of Cell Biology

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We have shown previously that epimorphin (EPM), a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which EPM mediates luminal morphogenesis. Treatment of cells with EPM to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein (C/EBP)β and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, since constitutive expression of LIP was sufficient to produce lumen formation, whereas constitutive expression of LAP blocked EPM-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which EPM expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPβ, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for EPM in luminal morphogenesis through control of C/EBPβ expression.

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Section: Epm Is a Member Of The Syntaxin Familymentioning

confidence: 99%

Epimorphin Mediates Mammary Luminal Morphogenesis through Control of C/EBPβ

Hirai

Radisky

Boudreau

et al. 2001

The Journal of Cell Biology

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“…Howchitta et al, 1991;Go ¨rlich et al, 1992; Go ¨rlich and Rapoever, a few proteins have been found that can exist in port, 1993). Reconstitution into liposomes of only two two or more topological forms (Skach et al, 1993;Dun-protein complexes, the receptor for the signal recognilop et Zhang and Ling, 1995;Levy, 1996). In tion particle (SRP) and Sec61 complex, is sufficient to most cases, the physiological significance of such obreproduce both translocation and membrane integration servations, or the mechanisms by which this occurs, of certain model proteins (Go ¨rlich and Rapoport, 1993; remain obscure.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Protein Topology by trans-Acting Factors at the Endoplasmic Reticulum

1998

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In mammalian cells, the Sec61 complex and translocating chain-associated membrane protein (TRAM) are necessary and sufficient to direct the biogenesis, in the appropriate topology, of all secretory and membrane proteins examined thus far. We demonstrate here that the proper translocation of the prion protein (PrP), a substrate that can be synthesized in more than one topologic form, requires additional factors. In the absence of these additional factors, PrP is synthesized exclusively in the transmembrane topology (termed the CtmPrP form) associated with the development of neurodegenerative disease. Thus, translocation accessory factors, acting on some but not other substrates, can function as molecular switches to redirect nascent proteins toward divergent topologic fates with different functional consequences.

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“…regulation of this unusual protein. It will be interesting to see whether the topology of PrP is regulated in vivo Similarly, the P-glycoprotein product of the multidrug resistance gene (MDR1) found in various cancer cells is by trans-acting cellular factors, and whether dysregulation of these events at the ER plays a role in any of the a membrane protein with at least two topological forms (Skach et al, 1993;Zhang et al, 1993). Although pre-wide variety of diseases attributed to PrP.…”

mentioning

confidence: 99%