Resumo (PT):
The complexity of the mammalian p53 pathway and protein kinase C (PKC) family has hampered the discrimination of the effect of PKC isoforms on p53 activity. Using yeasts co-expressing the human wild-type p53 and a mammalian PKC-α, -δ, -ε or -ζ, we showed a differential regulation of p53 activity and phosphorylation state by PKC isoforms. Whereas PKC-α reduced the p53-induced yeast growth inhibition and cell cycle arrest, PKC-δ and -ε enhanced the p53 activity through p53 phosphorylation, and PKC-ζ had no effect on p53. This work identified positive and negative p53 regulators which represent promising pharmacological targets in anti-cancer therapy.
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Keywords: p53; Protein kinase C isoform; Cell growth; Cell cycle; p53 phosphorylation; Yeast
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<a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T36-4XGBG2V-8&_user=2460038&_coverDate=11%2F19%2F2009&_rdoc=8&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%234938%232009%23994169977%231560345%23FLA%23display%23Volume)&_cdi=4938&_sort=d&_docanchor=&_ct=31&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=627da4a61a33de2ce8a224aeb6749e37&searchtype=a"> Texto integral</a>
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Abstract (EN):
The complexity of the mammalian p53 pathway and protein kinase C (PKC) family has hampered the discrimination of the effect of PKC isoforms on p53 activity. Using yeasts co-expressing the human wild-type p53 and a mammalian PKC-alpha, -delta, -epsilon or -zeta, we showed a differential regulation of p53 activity and phosphorylation state by PKC isoforms. Whereas PKC-alpha reduced the p53-induced yeast growth inhibition and cell cycle arrest, PKC-delta and -epsilon enhanced the p53 activity through p53 phosphorylation, and PKC-zeta had no effect on p53. This work identified positive and negative p53 regulators which represent promising pharmacological targets in anti-cancer therapy.
Idioma:
Inglês
Tipo (Avaliação Docente):
Científica
Nº de páginas:
7