NDLI: Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs

Content Provider	PubMed Central
Author	Ji, Xiaona Huang, Qiang Long, Yu Nussinov, Ruth Ma, Buyong
Copyright Year	2014
Abstract	p53 protein has about thirty phosphorylation sites located at the N- and C-termini and in the core domain. The phosphorylation sites are relatively less mutated than other residues in p53. To understand why and how p53 phosphorylation sites are rarely mutated in human cancer, using a bioinformatics approaches, we examined the phosphorylation site and its nearby flanking residues, focusing on the consensus phosphorylation motif pattern, amino-acid correlations within the phosphorylation motifs, the propensity of structural disorder of the phosphorylation motifs, and cancer mutations observed within the phosphorylation motifs. Many p53 phosphorylation sites are targets for several kinases. The phosphorylation sites match 17 consensus sequence motifs out of the 29 classified. In addition to proline, which is common in kinase specificity-determining sites, we found high propensity of acidic residues to be adjacent to phosphorylation sites. Analysis of human cancer mutations in the phosphorylation motifs revealed that motifs with adjacent acidic residues generally have fewer mutations, in contrast to phosphorylation sites near proline residues. p53 phosphorylation motifs are mostly disordered. However, human cancer mutations within phosphorylation motifs tend to decrease the disorder propensity. Our results suggest that combination of acidic residues Asp and Glu with phosphorylation sites provide charge redundancy which may safe guard against loss-of-function mutations, and that the natively disordered nature of p53 phosphorylation motifs may help reduce mutational damage. Our results further suggest that engineering acidic amino acids adjacent to potential phosphorylation sites could be a p53 gene therapy strategy.
Related Links	http://dx.doi.org/10.3390/ijms150813275
Ending Page	13298
Page Count	24
Starting Page	13275
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	8
Volume Number	15
Language	English
Publisher	MDPI
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	MDPI
Subject Keyword	Physical and Theoretical Chemistry Inorganic Chemistry Organic Chemistry Spectroscopy Molecular Biology Catalysis Computer Science Applications Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs

Battle Against Cancer: An Everlasting Saga of p53

PRRT2 Mutations Are Related to Febrile Seizures in Epileptic Patients

The Consequence of Oncomorphic TP53 Mutations in Ovarian Cancer

Identification of an AMPK Phosphorylation Site in Drosophila TSC2 (gigas) that Regulate Cell Growth

Long Non-Coding RNAs and p53 Regulation

Overexpression of MicroRNA-30b Improves Adenovirus-Mediated p53 Cancer Gene Therapy for Laryngeal Carcinoma

Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

Effect of Repetitive Lysine-Tryptophan Motifs on the Eukaryotic Membrane

Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs

Similar Documents

Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs

Battle Against Cancer: An Everlasting Saga of p53

PRRT2 Mutations Are Related to Febrile Seizures in Epileptic Patients

The Consequence of Oncomorphic TP53 Mutations in Ovarian Cancer

Identification of an AMPK Phosphorylation Site in Drosophila TSC2 (gigas) that Regulate Cell Growth

Long Non-Coding RNAs and p53 Regulation

Overexpression of MicroRNA-30b Improves Adenovirus-Mediated p53 Cancer Gene Therapy for Laryngeal Carcinoma

Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

Effect of Repetitive Lysine-Tryptophan Motifs on the Eukaryotic Membrane

Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs