Jayme R Gallegos

Oregon Health and Science University, Portland, Oregon, United States

Are you Jayme R Gallegos?

Claim your profile

Publications (5)17.65 Total impact

  • Source
    Mu-Shui Dai · Jayme R Gallegos · Hua Lu

    Full-text · Article · Oct 2008
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: p63 is a member of the p53 tumor suppressor family that is critical for epithelial differentiation and also has an important role in cancer progression. Currently, the molecular mechanisms governing regulation of p63 function remain largely unclear. This study identifies a unique E3 ubiquitin ligase for p63, SCFβTrCP1. SCFβTrCP1 is able to bind p63γ isoforms, with a higher affinity for the TAp63γ isoform. Strikingly, co-expression of TAp63γ and βTrCP1 leads to the stabilization of TAp63γ. This stabilization of TAp63γ leads to up-regulation of p21 at the mRNA and protein level by increased binding of TAp63γ at the p21 promoter. The up-regulation of p21 causes a subsequent increase in G1 phase cell cycle arrest. Last, SCFβTrCP1 is able to ubiquitylate TAp63γ, and this ubiquitylation, as well as the increased activity of TAp63γ, is ablated with the expression of a ubiquitin-deficient mutant of βTrCP1 (ΔFβTrCP1). Therefore, our study reveals that SCFβTrCP1 is an E3 ligase that activates p63 through ubiquitylation.
    Preview · Article · Feb 2008 · Journal of Biological Chemistry
  • [Show abstract] [Hide abstract]
    ABSTRACT: p63 is a member of the p53 tumor suppressor family that is critical for epithelial differentiation and also has an important role in cancer progression. Currently, the molecular mechanisms governing regulation of p63 function remain largely unclear. This study identifies a unique E3 ubiquitin ligase for p63, SCFβTrCP1. SCFβTrCP1 is able to bind p63γ isoforms, with a higher affinity for the TAp63γ isoform. Strikingly, co-expression of TAp63γ and βTrCP1 leads to the stabilization of TAp63γ. This stabilization of TAp63γ leads to up-regulation of p21 at the mRNA and protein level by increased binding of TAp63γ at the p21 promoter. The up-regulation of p21 causes a subsequent increase in G1 phase cell cycle arrest. Last, SCFβTrCP1 is able to ubiquitylate TAp63γ, and this ubiquitylation, as well as the increased activity of TAp63γ, is ablated with the expression of a ubiquitin-deficient mutant of βTrCP1 (ΔFβTrCP1). Therefore, our study reveals that SCFβTrCP1 is an E3 ligase that activates p63 through ubiquitylation.
    No preview · Article · Jan 2008 · Journal of Biological Chemistry
  • Source
    Mingjia Tan · Jayme R Gallegos · Qingyang Gu · Yuanhui Huang · Jun Li · Yetao Jin · Hua Lu · Yi Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: Skp1-cullin-F-box protein (SCF) is a multicomponent E3 ubiquitin (Ub) ligase that ubiquitinates a number of important biologic molecules such as p27, beta-catenin, and IkappaB for proteasomal degradation, thus regulating cell proliferation and survival. One SCF component, SAG/ROC2/Rbx2/Hrt2, a RING finger protein, was first identified as a redox-inducible protein, which, when overexpressed, inhibited apoptosis both in vitro and in vivo. We report here that sensitive to apoptosis gene (SAG), as well as its family member ROC1/Rbx1, bound to the proinactive form of caspase-3 (pro-caspase-3). Binding was likely mediated through F-box protein, beta-transducin repeat-containing protein (beta-TrCP), which binds to the first 38 amino acids of pro-caspase-3. Importantly, beta-TrCP1 expression significantly shortened the protein half-life of pro-caspase-3, whereas expression of a dominant-negative beta-TrCP1 mutant with the F-box domain deleted extended it. An in vitro ubiquitination assay showed that SAG/ROC-SCF(beta-TrCP) promoted ubiquitination of pro-caspase-3. Furthermore, endogenous levels of pro-caspase-3 were decreased by overexpression of SAG/ROC-SCF(beta-TrCP) E3 Ub ligases, but increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1), or beta-TrCPs, leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing ligand through increased activation of caspase-3. Thus, pro-caspase-3 appears to be a substrate of SAG/ROC-SCF(beta-TrCP) E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3.
    Preview · Article · Jan 2007 · Neoplasia (New York, N.Y.)
  • Source
    Mu-Shui Dai · Yetao Jin · Jayme R Gallegos · Hua Lu
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein ubiquitylation has been demonstrated to play a vital role not only in mediating protein turnover but also in modulating protein activity. The stability and activity of the tumor suppressor p53 and of the oncoprotein c-Myc are no exception. Both are regulated through independent ubiquitylation by several E3 ubiquitin ligases. Interestingly, p53 and c-Myc are functionally connected by some of these E3 enzymes and their regulator ARF, although these proteins play opposite roles in controlling cell growth and proliferation. The balance of this complex ubiquitylation network and its disruption during oncogenesis will be the topics of this review.
    Full-text · Article · Sep 2006 · Neoplasia (New York, N.Y.)

Publication Stats

128 Citations
17.65 Total Impact Points

Institutions

  • 2006-2008
    • Oregon Health and Science University
      • Department of Biochemistry & Molecular Biology
      Portland, Oregon, United States