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MDM2, MDMX and p53 in oncogenesis and cancer therapy
The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor. However, theExpand
Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis
Summary Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, isExpand
c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability.
Oncogene overexpression activates p53 by a mechanism posited to involve uncharacterized hyperproliferative signals. We determined whether such signals produce metabolic perturbations that generateExpand
The p53 orchestra: Mdm2 and Mdmx set the tone.
The activities of p53 cover diverse aspects of cell biology, including cell cycle control, apoptosis, metabolism, fertility, differentiation and cellular reprogramming. Although loss of p53 functionExpand
Hdmx Modulates the Outcome of P53 Activation in Human Tumor Cells*
Tumors that express wild-type P53 provide a target for therapies designed to reactivate P53 function. This is supported by the potent activation of P53 in tumor cells by Nutlin, a cis-imidazolineExpand
Targeted in vivo expression of the cyclin-dependent kinase inhibitor p21 halts hepatocyte cell-cycle progression, postnatal liver development and regeneration.
The CDK inhibitor p21 (WAF-1/CIP-1/SDI-1) has been implicated in DNA damage-induced p53-mediated G1 arrest, as well as in physiological processes, such as cell differentiation and senescence, that doExpand
A stapled p53 helix overcomes HDMX-mediated suppression of p53.
Cancer cells neutralize p53 by deletion, mutation, proteasomal degradation, or sequestration to achieve a pathologic survival advantage. Targeting the E3 ubiquitin ligase HDM2 can lead to aExpand
Targeting Mdm2 and Mdmx in Cancer Therapy: Better Living through Medicinal Chemistry?
  • M. Wade, G. Wahl
  • Biology, Medicine
  • Molecular Cancer Research
  • 1 January 2009
Genomic and proteomic profiling of human tumor samples and tumor-derived cell lines are essential for the realization of personalized therapy in oncology. Identification of the changes required forExpand
Quantitative analyses reveal the importance of regulated Hdmx degradation for P53 activation
P53 regulates numerous downstream targets to induce cell cycle arrest, senescence, apoptosis, and DNA repair in response to diverse stresses. Hdm2 and Hdmx are critical negative regulators of P53Expand
Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA
BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1.Expand