Hypoxia-inducible factors, mTOR, and astrin constitute an integrative regulatory network in colon cancer cells.

Astrin/SPAG5 is a mitotic spindle protein found to be overexpressed in several human cancers, functioning as an oncogene. The expression of Astrin has not been reported so far in colon cancer, nor has it been related to HIFs expression or action. Since mTOR, Astrin, and hypoxia-inducible factors (HIFs) are involved in promoting the growth and survival of cancer cells, we investigated the possible interaction between them in cultured colon cancer cells.

Protein phosphatase 2A B55β limits CD8+ T cell lifespan following cytokine withdrawal.

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55β, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55β induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal.

Functional Interaction of Hypoxia-Inducible Factor 2-Alpha and Autophagy Mediates Drug Resistance in Colon Cancer Cells.

Hypoxia and the accumulation of hypoxia-inducible factors (HIFs) in tumors have been associated with therapeutic resistance and with autophagy establishment. We examined the effects of stable knockdown of HIF-1α or HIF-2α expression on autophagy and drug resistance in colon cancer cells. We found that under normoxic conditions, malignant cells exhibit increased basal levels of autophagy, compared with non-malignant cells, in addition to the previously reported coexpression of HIF-1α and HIF-2α.

Identification of Dp71e, a new dystrophin with a novel carboxy-terminal end.

Several dystrophin Dp71 isoforms have previously been described and can be grouped into two subfamilies (Dp71d or Dp71f) depending upon the splicing of exon 78. As a consequence of this splicing, each group has a carboxy-terminal end with a unique amino acid composition; this composition imparts specific characteristics with respect to subcellular localization and interactions with particular members of the dystrophin-associated proteins (DAPs) complex. We have discovered a new alternative splicing event at the 3' region of the Dp71 transcript.