The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

[Acute promyelocytic leukemia, histone deacetylase, and response to retinoids]

Acute promyelocytic leukemia (APL) originate from chromosomal translocations generating two types of fusion proteins both involving the retinoic acid receptor alpha (RAR alpha) and either the gene PML (t(15;17)) or PLZF (t(11;17)). Recent publications cast a new light on the detailed molecular mechanism underlying the oncogenic activity of these fusion proteins which block myeloid terminal differentiation by recruiting histone deacetylases to the promoters of target genes through co-repressor proteins. They also explain the different responses to treatment by all-trans retinoic acid (ATRA) of these two variants which are otherwise clinically indistinguishable

[Acute promyelocytic leukemia, histone deacetylase, and response to retinoids]

Acute promyelocytic leukemia (APL) originate from chromosomal translocations generating two types of fusion proteins both involving the retinoic acid receptor alpha (RAR alpha) and either the gene PML (t(15;17)) or PLZF (t(11;17)). Recent publications cast a new light on the detailed molecular mechanism underlying the oncogenic activity of these fusion proteins which block myeloid terminal differentiation by recruiting histone deacetylases to the promoters of target genes through co-repressor proteins. They also explain the different responses to treatment by all-trans retinoic acid (ATRA) of these two variants which are otherwise clinically indistinguishable

[Acute promyelocytic leukemia, histone deacetylase, and response to retinoids]

Acute promyelocytic leukemia (APL) originate from chromosomal translocations generating two types of fusion proteins both involving the retinoic acid receptor alpha (RAR alpha) and either the gene PML (t(15;17)) or PLZF (t(11;17)). Recent publications cast a new light on the detailed molecular mechanism underlying the oncogenic activity of these fusion proteins which block myeloid terminal differentiation by recruiting histone deacetylases to the promoters of target genes through co-repressor proteins. They also explain the different responses to treatment by all-trans retinoic acid (ATRA) of these two variants which are otherwise clinically indistinguishable

[The role of APC in colonic cancerogenesis: zeroing in on Myc]

The APC gene is mutated both in familial adenomatous polyposis (FAP) and sporadic colorectal cancers. It had been previously shown that the APC gene product interacts with beta-catenin, a key element in the Wnt-1 signaling pathway. This pathway is initiated by the growth factor Wnt-1 and ends up in the nucleus where it activates transcription factors of the Lef/Tcf family although the targets of the latter were still unknown. This has just been accomplished by the identification of the c-MYC oncogene as the relevant target of the Wnt-1/APC pathway in the development of human colorectal cancers. Indeed, under appropriate conditions (presence of growth factors, for example), c-MYC is an essential determinant of cell proliferation