Next Article in Journal
A Review on Bioactivities of Tobacco Cembranoid Diterpenes
Next Article in Special Issue
Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K
Previous Article in Journal
Aurora A Protein Kinase: To the Centrosome and Beyond
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Biomolecules 2019, 9(1), 29; https://doi.org/10.3390/biom9010029

Impact of p85α Alterations in Cancer

1
Cancer Research Group, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada
2
Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada
3
Cancer Research, Saskatchewan Cancer Agency, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada
*
Author to whom correspondence should be addressed.
Received: 7 December 2018 / Revised: 7 January 2019 / Accepted: 11 January 2019 / Published: 15 January 2019
(This article belongs to the Special Issue Phosphoinositide 3-kinase, a Field in Transition)
Full-Text   |   PDF [4868 KB, uploaded 17 January 2019]   |  
  |   Review Reports

Abstract

The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in the regulation of cell signaling, proliferation, survival, migration and vesicle trafficking in normal cells and is frequently deregulated in many cancers. The p85α protein is the most characterized regulatory subunit of the class IA PI3Ks, best known for its regulation of the p110-PI3K catalytic subunit. In this review, we will discuss the impact of p85α mutations or alterations in expression levels on the proteins p85α is known to bind and regulate. We will focus on alterations within the N-terminal half of p85α that primarily regulate Rab5 and some members of the Rho-family of GTPases, as well as those that regulate PTEN (phosphatase and tensin homologue deleted on chromosome 10), the enzyme that directly counteracts PI3K signaling. We highlight recent data, mapping the interaction surfaces of the PTEN–p85α breakpoint cluster region homology (BH) domain, which sheds new light on key residues in both proteins. As a multifunctional protein that binds and regulates many different proteins, p85α mutations at different sites have different impacts in cancer and would necessarily require distinct treatment strategies to be effective. View Full-Text
Keywords: PI3K (phosphatidylinositol 3-kinase); cancer; mutations; p85α subunit; PTEN (phosphatase and tensin homologue deleted on chromosome 10); Rab5 PI3K (phosphatidylinositol 3-kinase); cancer; mutations; p85α subunit; PTEN (phosphatase and tensin homologue deleted on chromosome 10); Rab5
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Marshall, J.D.S.; Whitecross, D.E.; Mellor, P.; Anderson, D.H. Impact of p85α Alterations in Cancer. Biomolecules 2019, 9, 29.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top