Selective inhibition of nuclear steroid receptor function by a protein from a human tumorigenic poxvirus.
The poxvirus molluscum contagiosum (MC) has a worldwide distribution and its prevalence is on the rise. Here we report that the MCV MC013L protein inhibits glucocorticoid and vitamin D, but not retinoid or estrogen, nuclear receptor transactivation. A direct interaction of MC013L with glucocorticoid and vitamin D receptor is supported by yeast two-hybrid, GST pull-down, and far Western blot analyses. Glucocorticoids act as potent inhibitors of keratinocyte proliferation, while vitamin D and retinoids promote and block terminal differentiation, respectively. Therefore, MC013L may promote efficient virus replication by blocking the differentiation of infected keratinocytes. MC013L may be the first member of a new class of poxvirus proteins that directly modulate nuclear receptor-mediated transcription.
Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
N
N
Chen
T
T
Baudino
P N
PN
MacDonald
M
M
Green
W L
WL
Kelley
J W
JW
Burnett
R M
RM
Buller
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002117:Calcitriol / Q000378:metabolism; D002467:Cell Nucleus; D015870:Gene Expression; D017930:Genes, Reporter; D006133:Growth Substances / Q000235:genetics; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D008977:Molluscum contagiosum virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
D006133:Growth Substances; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D014764:Viral Proteins; D002117:Calcitriol