Papers by Yolanda Sánchez
Proceedings of The National Academy of Sciences, 2003
The transition from transcription initiation to elongation involves phosphorylation of the large ... more The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1␣ (HIF-1␣) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-␣ and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylationdependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation.
Molecular and Cellular Biology, 2004
The retinoblastoma protein (Rb)/E2F pathway links cellular proliferation control to apoptosis and... more The retinoblastoma protein (Rb)/E2F pathway links cellular proliferation control to apoptosis and is critical for normal development and cancer prevention. Here we define a transcription-mediated pathway in which deregulation of E2F1 by ectopic E2F expression or Rb inactivation by E7 of human papillomavirus type 16 signals apoptosis by inducing the expression of Chk2, a component of the DNA damage response. E2F1-and E7-mediated apoptosis are compromised in cells from patients with the related disorders ataxia telangiectasia and Nijmegen breakage syndrome lacking functional Atm and Nbs1 gene products, respectively. Both Atm and Nbs1 contribute to Chk2 activation and p53 phosphorylation following deregulation of normal Rb growth control. E2F2, a related E2F family member that does not induce apoptosis, also activates Atm, resulting in phosphorylation of p53. However, we found that the key commitment step in apoptosis induction is the ability of E2F1, and not E2F2, to upregulate Chk2 expression. Our results suggest that E2F1 plays a central role in signaling disturbances in the Rb growth control pathway and, by upregulation of Chk2, may sensitize cells to undergo apoptosis.
Planta Medica, 1996
Four sesquiterpenoids, beta-caryophyllene, beta-caryophyllene 4,5 alpha-oxide, 7-hydroxy-3,4-dihy... more Four sesquiterpenoids, beta-caryophyllene, beta-caryophyllene 4,5 alpha-oxide, 7-hydroxy-3,4-dihydrocadalin, and 7-hydroxycadalin, isolated from the dried flower of Heterotheca inuloides Cass. (Asteraceae), have been found to exhibit cytotoxic activity against several solid tumor cell lines. Among them, 7-hydroxy-3,4-dihydrocadalin and 7-hydroxycadalin have also been found to inhibit autoxidative and microsomal lipid peroxidation.
Bioorganic & Medicinal Chemistry, 1997
Sesquiterpenoids, 7-hydroxy-3,4-dihydrocadalin and 7-hydroxycadalin, and flavonoids, quercetin, k... more Sesquiterpenoids, 7-hydroxy-3,4-dihydrocadalin and 7-hydroxycadalin, and flavonoids, quercetin, kaempferol and their glycosides, isolated from Heterotheca inuloides (Asteraceae), a Mexican medicinal plant known as "arnica", were evaluated as antioxidants. These compounds showed potent scavenging activity on diphenyl-p-picrylhydrazyl (DPPH) radical. Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH was inhibited by both terpenoids and flavonoids, though only flavonoids possessed superoxide anion scavenging activity in microsome. Flavonoids also scavenged enzymatically and non-enzymatically generated superoxide anion. On the other hand, mitochondrial lipid peroxidation induced by Fe(III)-ADP/NADH was inhibited only by sesquiterpenoids. Furthermore, these terpenes protected mitochondrial enzyme activity against oxidative stress. These results showed that two types of antioxidants existed in the dried flower of H. inuloides and would contribute to protection of tissues against various oxidative stresses.
Bioorganic & Medicinal Chemistry, 2000
AbstractÐTyrosinase inhibitory activity of¯avonols, galangin, kaempferol and quercetin, was found... more AbstractÐTyrosinase inhibitory activity of¯avonols, galangin, kaempferol and quercetin, was found to come from their ability to chelate copper in the enzyme. In contrast, the corresponding¯avones, chrysin, apigenin and luteolin, did not chelate copper in the enzyme. The chelation mechanism seems to be speci®c to¯avonols as long as the 3-hydroxyl group is free. Interestingly,¯avonols aect the enzyme activity in dierent ways. For example, quercetin behaves as a cofactor and does not inhibit monophenolase activity. On the other hand, galangin inhibits monophenolase activity and does not act as a cofactor. Kaempferol neither acts as a cofactor nor inhibits monophenolase activity. However, these three¯avonols are common to inhibit diphenolase activity by chelating copper in the enzyme. #
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Papers by Yolanda Sánchez