Two arms of TGF? signaling
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《细胞学杂志》
Cancer-associated overproliferation is thwarted in many cell types by transforming growth factor ? (TGF?), which turns on p21(WAF1/CIP1) cell cycle inhibitors via Smad transcription factors. On page 979, Sakaguchi et al. show that TGF?'s arsenal in its antiproliferation crusade is larger than just the Smads—a calcium-binding protein called S100C/A11 also responds to the call of duty.
The group previously showed that high extracellular Ca2+ results in phosphorylation of cytoplasmic S100C/A11, driving it into the nucleus. Once there, it releases the transcription factor Sp1 from its binding partner, nucleolin, so that Sp1 can activate p21(WAF1/CIP1) transcription to halt division in skin cells.
The new results demonstrate that this S100C/A11 pathway requires PKC-mediated phosphorylation of S100C/A11 and, like the Smad pathway, is triggered by TGF?. Both branches are needed to stop skin cell growth in response to TGF?.
Sp1 turns on many genes, not just those for cell cycle inhibitors. Specificity may be conferred by Sp1's known binding to Smads. This suggests that the two branches of the TGF? pathway may come together at their end point, making this pathway resemble not so much a branch as a brace of parentheses.(S100C/A11 (red) moves to the nucleus whe)
The group previously showed that high extracellular Ca2+ results in phosphorylation of cytoplasmic S100C/A11, driving it into the nucleus. Once there, it releases the transcription factor Sp1 from its binding partner, nucleolin, so that Sp1 can activate p21(WAF1/CIP1) transcription to halt division in skin cells.
The new results demonstrate that this S100C/A11 pathway requires PKC-mediated phosphorylation of S100C/A11 and, like the Smad pathway, is triggered by TGF?. Both branches are needed to stop skin cell growth in response to TGF?.
Sp1 turns on many genes, not just those for cell cycle inhibitors. Specificity may be conferred by Sp1's known binding to Smads. This suggests that the two branches of the TGF? pathway may come together at their end point, making this pathway resemble not so much a branch as a brace of parentheses.(S100C/A11 (red) moves to the nucleus whe)