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Biochemistry (Moscow)

, Volume 75, Issue 13, pp 1692–1721 | Cite as

Constitutive and induced functions of the p53 gene

  • A. O. Zheltukhin
  • P. M. ChumakovEmail author
Review

Abstract

The p53 tumor suppressor serves to secure genetic stability of multicellular organisms. It suppresses the accumulation of mutations in somatic cells and substantially decreases the probability of malignant diseases. The p53 gene acts highly selectively through multiple mechanisms. Under relatively favorable conditions, p53 helps to maintain intracellular homeostasis by balancing anabolic and catabolic processes and by timely elimination of reactive oxygen species. These functions of p53 facilitate maximal efficiency and survival of cells under conditions of physiological stresses. In the case of grave molecular damage caused by severe stress, a significant amount of highly active p53 is induced leading to irreversible growth arrest and programmed cell death. The induced functions of p53 secure the timely elimination from the organism of damaged and potentially dangerous cells. Collectively, the functions of p53 contribute to the prevention of malignant and other diseases and decelerate the aging process.

Key words

p53 tumor suppressor cancer prevention signal transduction molecular damage aging apoptosis autophagy cell cycle control oncogenes tumor suppressor genes 

Abbreviations

Akt

protein kinase B and its gene

AMPK

AMP-dependent kinase

GSK3β

glycogen synthase kinase encoding gene

IGF-1

insulin-like growth factor

iPS

induced pluripotent stem cells

clonogenic index

number of clones formed upon plating 100 cells per dish

LKB1

gene encoding AMPK-activating PK and several different kinases

MDM2

gene encoding Mdm2 protein, ubiquitin E3 class ligase involved in protein p53 stability regulation

mTOR

mammalian and human TOR homolog

NA

nucleic acids; nutlins (from Nutley, a small town in the USA where a Hoffman-LaRoche company facility is located), small molecules able to destroy complex of p53 and Mdm2 proteins

PIP2 and PIP3

phosphatidylinositol bis-phosphate and phosphatidylinositol triphosphate

PK

protein kinase

pRB

product of retinoblastoma suppressor gene

PTEN

tumor suppressor encoding “tensin-homologous protein phosphatase”

ROS

reactive oxygen species

TOR

protein kinase target of rapamycin

TORC1

first TOR-containing kinase complex

TORC2

second TOR-containing kinase complex

TSC1

tuberin, product of TSC1 suppressor gene damaged in hereditary tuberous sclerosis

TSC2

hamartin, product of TSC2 suppressor gene damaged in hereditary tuberous sclerosis

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© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia

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