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Attention Score in Context
| Title |
Structural basis of PML/RARA oncoprotein targeting by arsenic unravels a cysteine rheostat controlling PML body assembly and function
|
|---|---|
| Published in |
Cancer Discovery, September 2023
|
| DOI | 10.1158/2159-8290.cd-23-0453 |
| Pubmed ID | |
| Authors |
Pierre Bercier, Qian Qian Wang, Ning Zang, Jie Zhang, Chang Yang, Yasen Maimaitiyiming, Majdouline Abou-Ghali, Caroline Berthier, Chengchen Wu, Michiko Niwa-Kawakita, Thassadite Dirami, Marie-Claude Geoffroy, Omar Ferhi, Samuel Quentin, Shirine Benhenda, Yasumitsu Ogra, Zoher Gueroui, Chun Zhou, Hua Naranmandura, Hugues de The, Valerie Lallemand-Breitenbach |
| Abstract |
PML Nuclear Bodies (NBs) are disrupted in PML-RARA-driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% APL patients, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that PML NBs display some features of liquid-liquid phase separation and that ATO induces a gel-like transition. PML B-box-2 structure reveals an alpha helix driving B2 trimerization and positioning a cysteine trio to form an ideal arsenic-binding pocket. Altering either of the latter impedes ATO-driven NB-assembly, PML sumoylation and PML-RARA degradation, mechanistically explaining clinical ATO-resistance. This B2 trimer and the C213 trio create an oxidation-sensitive rheostat that controls PML NB assembly dynamics and downstream signaling in both basal state and during stress response. These findings identify the structural basis for arsenic targeting of PML which could pave the way to novel cancer drugs. |
Twitter Demographics
The data shown below were collected from the profiles of 204 tweeters who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 10 | 5% |
| Netherlands | 10 | 5% |
| Japan | 6 | 3% |
| United States | 4 | 2% |
| Singapore | 2 | <1% |
| China | 2 | <1% |
| Australia | 1 | <1% |
| Saudi Arabia | 1 | <1% |
| Pakistan | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 167 | 82% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 189 | 93% |
| Scientists | 9 | 4% |
| Science communicators (journalists, bloggers, editors) | 1 | <1% |
| Unknown | 5 | 2% |
Attention Score in Context
This research output has an Altmetric Attention Score of 218. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 September 2023.
All research outputs
#167,260
of 24,520,935 outputs
Outputs from Cancer Discovery
#57
of 3,918 outputs
Outputs of similar age
#2,253
of 260,757 outputs
Outputs of similar age from Cancer Discovery
#3
of 82 outputs
Altmetric has tracked 24,520,935 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,918 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.2. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 260,757 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 82 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.