TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis.

Ste20-related proline-alanine-rich kinase (SPAK) has been linked to various cellular processes, including proliferation, differentiation, and ion transport regulation. Recently, we showed that SPAK mediates signaling by the TNF receptor, RELT. The presence of a caspase cleavage site in SPAK prompted us to study its involvement in apoptotic signaling induced by another TNF member, TRAIL.

The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK activation.

Receptor expressed in lymphoid tissues (RELT) is a new member of the TNFR family with little known regarding its signaling. Typically, TNFRs engage TRAFs for activation of NF-kappaB and MAPK cascades. We found that RELT does not use the standard signaling pathways characteristic of other TNFRs.

TWEAK mediates signal transduction and differentiation of RAW264.7 cells in the absence of Fn14/TweakR. Evidence for a second TWEAK receptor.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor family that is implicated in apoptosis, proliferation, migration, and inflammation. We describe our findings showing that TWEAK mediated the differentiation of RAW264.7 (RAW) monocyte/macrophage cells into multinuclear, functional osteoclasts.

p53 Is required for 1,25-dihydroxyvitamin D3-induced G0 arrest but is not required for G1 accumulation or apoptosis of LNCaP prostate cancer cells.

1,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is an effective agent for inhibiting the growth of prostate cancer cells including LNCaP and PC-3 cell lines. However, the extent of growth inhibition in these cell lines differs because LNCaP cells are much more responsive than PC-3 cells. Previous studies in LNCaP cells have shown that 1,25-(OH)(2)D(3) treatment results in G(0)/G(1) cell cycle accumulation, loss of Ki67 expression, and induction of apoptosis.

Vitamin D and prostate cancer.

The original hypothesis of Schwartz and Hulka (1990) proposing that vitamin D deficiency may be a risk factor for prostate cancer has triggered many studies. Epidemiological studies have supported this hypothesis with findings that sunlight exposure is inversely proportional to prostate cancer mortality and that prostate cancer risk is greater in men with lower levels of vitamin D (Hanchette and Schwartz, 1992; Corder et al, 1993; Ahonen et al, 2000). Prostate cancer cells express receptors for 1,25(OH)2D3 and some cell lines are growth inhibited when treated with 1,25(OH)2D3 (reviewed in Blutt and Weigel, 1999).