Researchers and colleagues identify PHF20, a regulator of gene P53
Researchers at Moffitt Cancer Center and colleagues have identified PHF20, a novel transcriptional factor, and clarified its role in maintaining the stability and transcription of p53, a gene that allows for both normal cell growth and tumor suppression. PHF20, the researchers found, plays a previously unknown and unique role in regulating p53.
When p53 is activated, it can mend DNA damage and eliminate cancer cells by binding to DNA. How p53 maintains its basal level and becomes activated remain elusive, but identifying transcription factor PHF20 and understanding its interaction with p53 and its induction of p53 protein stability and transcription has provided a clue.
Results of their research appeared in a recent issue of Nature Structural & Molecular Biology and also in The Journal of Biological Chemistry.
"When a cell undergoes alterations that predispose it to become cancerous, p53 is activated to either mend the DNA damage or eliminate the affected cells, thereby preventing the development of tumors," said Jin Q. Cheng, Ph.D., M.D., a senior member of the Molecular Oncology Department and Molecular Oncology and Drug Discovery Program at Moffitt. "A number of mechanisms normally keep a regulatory strong check on p53 and allow for rapid activation. Still much is unknown about the mechanism of p53 regulation."
After identifying PHF20 as a novel transcriptional factor, the researchers set out in subsequent studies to probe the function of human PHF20 and its effect on p53. They found that PHF20 not only transcriptionally induces p53 but also directly interacts with and stabilizes p53. Akt negatively regulates these processes by interaction and phosphorylation of PHF20.
To determine whether the absence of PHF20 might regulate stress-induced p53 expression, the researchers "knocked down" PHF20. In doing so, they demonstrated that in the absence of PHF20, p53 was reduced. These findings established the role of PHF20 as a key regulator of p53 and additional link between Akt and p53.
According to Cheng, the identification of PHF20 as a regulator of p53 is significant because PHF20 "participates in simultaneous multiple interactions with other proteins and DNA" and serves to stabilize and induce p53.
"Regulation of p53 is critical to allow both normal cell growth and tumor suppression," explained Cheng. "However, further investigation is required to understand PHF20 tumor suppressor function and its possible involvement in human malignancy."
- Effect of mutant p53 stability on tumorigenesis and drug design May 15, 2008 | not rated yet | 0
- Three is the magic number: A chain reaction required to prevent tumor formation Jan 20, 2012 | not rated yet | 0
- Cancer is a p53 protein aggregation disease Mar 29, 2011 | not rated yet | 0
- Stabilizing cancer-fighting p53 can also shield a metastasis-promoter May 22, 2008 | not rated yet | 0
- Chemopreventive isothiocyanates selectively depletes mutant p53 in tumor cells Apr 20, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
9 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Treating pediatric leukemia patients with a liposomal formulation of anthracycline-based chemotherapy at a more intense-than-standard dose during initial treatment may result in high survival rates without causing any added ...
Cancer 50 minutes ago | not rated yet | 0
Scientists have uncovered a survival mechanism that occurs in breast cells that have just turned premalignant-cells on the cusp between normalcy and cancers-which may lead to new methods of stopping tumors.
Cancer 1 hour ago | not rated yet | 0 |
Frequent heartburn was positively associated with cancers of the throat and vocal cord among nonsmokers and nondrinkers, and the use of antacids, but not prescription medications, had a protective effect, according to data ...
Cancer 1 hour ago | not rated yet | 0
Aggressive forms of bladder cancer involve the protein PODXL – a discovery that could hold the key to improved treatment, according to researchers at Lund University, Uppsala University and KTH in Sweden.
Cancer 3 hours ago | 5 / 5 (1) | 0
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
59 minutes ago | 5 / 5 (2) | 0 |
Gaucher disease causes debilitating and sometimes fatal neurodegeneration in early childhood. Recent studies have uncovered a link between the mutations responsible for Gaucher disease and an increased risk ...
46 minutes ago | not rated yet | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
53 minutes ago | not rated yet | 0
Family caregivers of older adults with dementia are less stressed and their moods are improved on days when dementia patients receive adult day services (ADS), according to Penn State researchers.
50 minutes ago | not rated yet | 0
A new coronavirus has now claimed 22 lives worldwide out of 44 lab-confirmed cases, mostly in Saudi Arabia, World Health Organization officials said Thursday.
45 minutes ago | not rated yet | 0