Exploring the multiple roles of guardian of the genome: P53

被引:85
作者
Feroz, Wasim [1 ]
Sheikh, Arwah Mohammad Ali [2 ]
机构
[1] Vignan Inst Pharmaceut Technol, Dept Pharm Practice, Fac Pharm, Visakhapatnam, Andhra Pradesh, India
[2] Forum Business Res, Patient Experience Management, Visakhapatnam, Andhra Pradesh, India
关键词
TP53; Tumour suppressor protein P53; Apoptosis; DNA repair; Cellular senescence; DNA-DAMAGE RESPONSE; TUMOR-SUPPRESSOR; MUTANT P53; CELL-DEATH; TRANSCRIPTIONAL ACTIVATION; WILD-TYPE; TETRAMERIZATION DOMAIN; RHEUMATOID-ARTHRITIS; APOPTOTIC RESPONSE; CRYSTAL-STRUCTURE;
D O I
10.1186/s43042-020-00089-x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background Cells have evolved balanced mechanisms to protect themselves by initiating a specific response to a variety of stress. The TP53 gene, encoding P53 protein, is one of the many widely studied genes in human cells owing to its multifaceted functions and complex dynamics. The tumour-suppressing activity of P53 plays a principal role in the cellular response to stress. The majority of the human cancer cells exhibit the inactivation of the P53 pathway. In this review, we discuss the recent advancements in P53 research with particular focus on the role of P53 in DNA damage responses, apoptosis, autophagy, and cellular metabolism. We also discussed important P53-reactivation strategies that can play a crucial role in cancer therapy and the role of P53 in various diseases. Main body We used electronic databases like PubMed and Google Scholar for literature search. In response to a variety of cellular stress such as genotoxic stress, ischemic stress, oncogenic expression, P53 acts as a sensor, and suppresses tumour development by promoting cell death or permanent inhibition of cell proliferation. It controls several genes that play a role in the arrest of the cell cycle, cellular senescence, DNA repair system, and apoptosis. P53 plays a crucial role in supporting DNA repair by arresting the cell cycle to purchase time for the repair system to restore genome stability. Apoptosis is essential for maintaining tissue homeostasis and tumour suppression. P53 can induce apoptosis in a genetically unstable cell by interacting with many pro-apoptotic and anti-apoptotic factors. Furthermore, P53 can activate autophagy, which also plays a role in tumour suppression. P53 also regulates many metabolic pathways of glucose, lipid, and amino acid metabolism. Thus under mild metabolic stress, P53 contributes to the cell's ability to adapt to and survive the stress. Conclusion These multiple levels of regulation enable P53 to perform diversified roles in many cell responses. Understanding the complete function of P53 is still a work in progress because of the inherent complexity involved in between P53 and its target proteins. Further research is required to unravel the mystery of this Guardian of the genome "TP53".
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页数:23
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共 156 条
  • [51] Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death
    Gao, W.
    Shen, Z.
    Shang, L.
    Wang, X.
    [J]. CELL DEATH AND DIFFERENTIATION, 2011, 18 (10) : 1598 - 1607
  • [52] DNA polymerases that propagate the eukaryotic DNA replication fork
    Garg, P
    Burgers, PMJ
    [J]. CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2005, 40 (02) : 115 - 128
  • [53] Goldstein I, 2013, CANCER METAB, V1, DOI 10.1186/2049-3002-1-9
  • [54] Wip1 phosphatase: between p53 and MAPK kinases pathways
    Goloudina, Anastasia R.
    Kochetkova, Elena Y.
    Pospelova, Tatyana V.
    Demidov, Oleg N.
    [J]. ONCOTARGET, 2016, 7 (21) : 31563 - 31571
  • [55] Cytoplasmic functions of the tumour suppressor p53
    Green, Douglas R.
    Kroemer, Guido
    [J]. NATURE, 2009, 458 (7242) : 1127 - 1130
  • [56] Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment
    Gupta, Amit
    Shah, Karan
    Oza, Manisha J.
    Behl, Tapan
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2019, 109 : 484 - 492
  • [57] The multiple mechanisms that regulate p53 activity and cell fate
    Hafner, Antonina
    Bulyk, Martha L.
    Jambhekar, Ashwini
    Lahav, Galit
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2019, 20 (04) : 199 - 210
  • [58] Transcription-coupled DNA repair: two decades of progress and surprises
    Hanawalt, Philip C.
    Spivak, Graciela
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (12) : 958 - 970
  • [59] TP53 mutation hits energy metabolism and increases glycolysis in breast cancer
    Harami-Papp, Hajnalka
    Pongor, Lorinc S.
    Munkacsy, Gyongyi
    Horvath, Gergo
    Nagy, Adam M.
    Ambrus, Attila
    Hauser, Peter
    Szabo, Andras
    Tretter, Laszlo
    Gyorffy, Balazs
    [J]. ONCOTARGET, 2016, 7 (41) : 67183 - 67195
  • [60] The p53 pathway: positive and negative feedback loops
    Harris, SL
    Levine, AJ
    [J]. ONCOGENE, 2005, 24 (17) : 2899 - 2908