All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA. Consequently, CMA substrate proteins catalyze the glycolysis which contributes to the Warburg effect in cancer cells. The fact that the degradation of substrate proteins based on the CMA can be altered by posttranslational modifications such as phosphorylation or acetylation. In conclusion, targeting to CMA substrate proteins develops into a new anticancer therapeutic approach.

Transient expression of viral genes from certain poxviruses in uninfected mammalian cells can sometimes be unexpectedly inefficient. The reasons for poor expression levels can be due to a number of features of the gene cassette, such as cryptic splice sites, polymerase II termination sequences or motifs that lead to mRNA instability. Here we suggest that in some cases the problem of low protein expression in transfected mammalian cells may be due to inefficient codon usage. We have observed that for many poxvirus genes from the yatapoxvirus genus this deficiency can be overcome by synthesis of the gene with codon sequences optimized for expression in primate cells. This led us to examine colon usage across 2-dozen sequenced members of the Poxviridae. We conclude that codon usage is surprisingly divergent across the different Poxviridae genera but is much more conserved within a single genus. Thus, Poxviridae genera can be divided into distinct groups based on their observed codon bias. When viewed in this context, successful transient expression of transfected poxvirus genes in uninfected mammalian cells can be more accurately predicted based on codon bias. As a corollary, for specific poxvirus genes with less favorable codon usage, codon optimization can result in profoundly increased transient expression levels following transfection of uninfected mammalian cell lines.

Fundamental differences between meiosis and mitosis suggest that the shared central cell cycle machinery may be regulated differently during the two division cycles. This paper focuses on unique features of Cdc25C protein function during meiotic progression. We report on the existence of oocyte-specific CDC25C transcripts that differ from their somatic counterparts in the 3' untranslated region. While CDC25C mRNA levels remain constant in fully-grown oocytes, corresponding protein levels increase progressively during maturation to a maximum at metaphase II. Elevation of Cdc25C protein levels in G2-oocytes by mRNA injection failed to increase MPF-kinase levels or to induce premature entry into M-phase. Likewise, antisense-induced arrest of translation (translational arrest) had no effect on chromosome condensation, nucleolar disassembly, or nuclear membrane contraction. By contrast, translational arrest inhibited subsequent events including membrane disassembly and spindle formation. Neither up- nor down-regulation of Cdc25C synthesis after metaphase I plate formation influenced progression to metaphase II. However, translational arrest during metaphase resulted in incomplete chromosome decondensation and abnormal pronuclear membrane assembly after activation. We conclude that Cdc25 protein, translated from unique transcripts, is preferentially located in the oocyte nucleus and is essential for progress through late diakinesis. Subsequently, new synthesis of Cdc25C protein is required for the orderly transition from meiotic to mitotic cell division.

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