Jennifer D Kubic

Publications (2)9.35 Total impact

• Source

  Available from: Don Wolfgeher

  Article: GSK-3 promotes cell survival, growth, and PAX3 levels in human melanoma cells.

  Jennifer D Kubic, Joseph B Mascarenhas, Takumi Iizuka, Don Wolfgeher, Deborah Lang
  [show abstract] [hide abstract]
  ABSTRACT: GSK-3 is a serine/threonine kinase involved in a diverse range of cellular processes. GSK-3 exists in two isoforms, GSK-3α and GSK-3β, which possess some functional redundancy but also play distinct roles depending on developmental and cellular context. In this article, we found that GSK-3 actively promoted cell growth and survival in melanoma cells, and blocking this activity with small-molecule inhibitor SB216763 or gene-specific siRNA decreased proliferation, increased apoptosis, and altered cellular morphology. These alterations coincided with loss of PAX3, a transcription factor implicated in proliferation, survival, and migration of developing melanoblasts. We further found that PAX3 directly interacted with and was phosphorylated in vitro on a number of residues by GSK-3β. In melanoma cells, direct inhibition of PAX3 lead to cellular changes that paralleled the response to GSK-3 inhibition. Maintenance of PAX3 expression protected melanoma cells from the anti-tumor effects of SB216763. These data support a model wherein GSK-3 regulates proliferation and morphology of melanoma through phosphorylation and increased levels of PAX3.
  Molecular Cancer Research 06/2012; 10(8):1065-76. · 4.29 Impact Factor
• Article: Pigmentation PAX-ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease.

  Jennifer D Kubic, Kacey P Young, Rebecca S Plummer, Anton E Ludvik, Deborah Lang
  [show abstract] [hide abstract]
  ABSTRACT: Transcription factors initiate programs of gene expression and are catalysts in downstream molecular cascades that modulate a variety of cellular processes. Pax3 is a transcription factor that is important in the melanocyte and influences melanocytic proliferation, resistance to apoptosis, migration, lineage specificity and differentiation. In this review, we focus on Pax3 and the molecular pathways that Pax3 is a part of during melanogenesis and in the melanocyte stem cell. These roles of Pax3 are emphasized during the development of diseases and syndromes resulting from either too much or too little Pax3 function. Due to its key task in melanocyte stem cells and tumors, the Pax3 pathway may provide an ideal target for either stem cell or cancer therapies.
  Pigment Cell & Melanoma Research 11/2008; 21(6):627-45. · 5.06 Impact Factor