Mitogen signaling strength and duration can control cell cycle decisions

R Nussinov, W Zhang, Y Liu, H Jang - Science Advances, 2024‏ - science.org
Decades ago, mitogen-promoted signaling duration and strength were observed to be
sensed by the cell and to be critical for its decisions: to proliferate or differentiate. Landmark …

[HTML][HTML] Cell phenotypes can be predicted from propensities of protein conformations

R Nussinov, Y Liu, W Zhang, H Jang - Current opinion in structural biology, 2023‏ - Elsevier
Proteins exist as dynamic conformational ensembles. Here we suggest that the propensities
of the conformations can be predictors of cell function. The conformational states that the …

Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome

BR Yavuz, MK Arici, HC Demirel, CJ Tsai… - NPJ genomic …, 2023‏ - nature.com
Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs)
are more prone to develop certain types of cancer. Notably, however, the case statistics can …

Molecular principles underlying aggressive cancers

R Nussinov, BR Yavuz, H Jang - Signal Transduction and Targeted …, 2025‏ - nature.com
Aggressive tumors pose ultra-challenges to drug resistance. Anti-cancer treatments are
often unsuccessful, and single-cell technologies to rein drug resistance mechanisms are still …

SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities

Y Liu, W Zhang, H Jang, R Nussinov - Cellular and Molecular Life …, 2024‏ - Springer
SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its
mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders …

Ubiquitin E3 ligases assisted technologies in protein degradation: Sharing pathways in neurodegenerative disorders and cancer

A Kaushik, S Parashar, RK Ambasta, P Kumar - Ageing Research Reviews, 2024‏ - Elsevier
E3 ligases, essential components of the ubiquitin-proteasome-mediated protein degradation
system, play a critical role in cellular regulation. By covalently attaching ubiquitin (Ub) …

Slower CDK4 and faster CDK2 activation in the cell cycle

W Zhang, Y Liu, H Jang, R Nussinov - Structure, 2024‏ - cell.com
Dysregulation of cyclin-dependent kinases (CDKs) impacts cell proliferation, driving cancer.
Here, we ask why the cyclin-D/CDK4 complex governs cell cycle progression through the …

[HTML][HTML] Cancer and autism: how PTEN mutations degrade function at the membrane and isoform expression in the human brain

H Jang, J Chen, LM Iakoucheva, R Nussinov - Journal of Molecular Biology, 2023‏ - Elsevier
Mutations causing loss of PTEN lipid phosphatase activity can promote cancer, benign
tumors (PHTS), and neurodevelopmental disorders (NDDs). Exactly how they preferentially …

Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide

R Nussinov, BR Yavuz, HC Demirel, MK Arici… - Frontiers in Cell and …, 2024‏ - frontiersin.org
The connection and causality between cancer and neurodevelopmental disorders have
been puzzling. How can the same cellular pathways, proteins, and mutations lead to …

The allosteric mechanism of mTOR activation can inform bitopic inhibitor optimization

Y Liu, M Zhang, H Jang, R Nussinov - Chemical Science, 2024‏ - pubs.rsc.org
mTOR serine/threonine kinase is a cornerstone in the PI3K/AKT/mTOR pathway. Yet, the
detailed mechanism of activation of its catalytic core is still unresolved, likely due to mTOR …