PNAS: Discover that the Terminator protein can stop cancer cells!

, June 20, 2020 /
BiovalleyBIOON/-- The basic process of mammalian cells is controlled by a protein called transcription factorsFor example, a low-oxygen environment triggers the transcription factor HIF-1, which adapts cells to hypoxiatranscription factors work in healthy cells, cancer cells can use transcription factors such as HIF-1 to promote the growth oftumor
A new studyhening Lin, a professor of chemistry and chemical biology at Cornell University's School of Arts and Sciences, found that a protein called TiPARP can act as a terminator of a variety of cancer-causing transcription factors, including HIF-1, which is associated with many cancers, includingbreast cancerTherefore, the study shows that TiPARP is a cancer-suppressing genephoto source: NIHpaper "TiPARP Forms Nuclear Scondensates to Quee HIF-1 and Suppress Tumorigenesis", published in The Niah, establishes the closing mechanism of TiPARP as several important transcription factors, including HIF-1, C0-Myc and estrogen receptors, and shows how TiPARP itself degrades in the processThe study also revealed the mechanism by which TiPARP terminates these factors, another new findingLin says HIF-1 is important for cancer because manytumorsgrow in low oxygen conditions "
In order for these tumors to survive, they have to rely on HIF-1," Lin said "TiPARP is the Terminator of HIF-1 Therefore, if TiPARP can be activated, it can inhibit the growth of tumor "
Lin and co-founders are also excited about the discovery of the mechanism by TiPARP that causes the termination of HIF-1 and other transcription factors This mechanism, known as liquid-liquid phase separation or phase condensation, is a very interesting topic in biology imagine vinegar dripping in the oil: vinegar forms a distinct drop letdrop in the sticky oil similarly, when TiPARP is activated in the nucleus, it forms so-called "phase separation" in which HIF-1-alpha and HUWE1 (a ubiquitin-linked enzyme) are recruited in the nucleus This initiates the process of simultaneous inactivation and degradation of HIF-1-alpha and TiPARP Lin says that through phase separation, TiPARP not only terminates HIF-1, but also several different transcription factors associated with different types of cancer in fact, TiPARP may have played a role in it, moxifen, a widely used breast cancer drug Lin believes alpha is successful in treating estrogen-receptor-positive breast cancer because TiPARP actively terminates estrogen receptors, HIF-1 and c-Myc in tumor "When it comes to moxifen and similar compounds being developed as estrogen receptor agonists or antagonists, we don't even know which compound would be better," he said "Now our idea is, which compound is better able to activate TiPARP?" (BioValleyBioon.com) References: Lu Zhang et al, TiPARP Forms nuclear condensates to quee HIF-1 alpha and suppress thorionis, proceedings of the National Academy of Sciences (2020) DOI: 10.1073/pnas.1921815117 .