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Review
. 2011 Sep;137(9):1283-7.
doi: 10.1007/s00432-011-0996-y. Epub 2011 Jun 26.

TRAIL and guardian angel of genome integrity: ATM boards TRAIL blazer

Ammad Ahmad Farooqi  1 , Salman Waseem, Muhammad Sajjad Ashraf, Muhammed Javed Iqbal, Shahzad Bhatti
Affiliations
Review

TRAIL and guardian angel of genome integrity: ATM boards TRAIL blazer

Ammad Ahmad Farooqi et al. J Cancer Res Clin Oncol. 2011 Sep.

Abstract

Prostate cancer is a multifaceted progressive multistep disorder that arises because of accumulation of genetic and epigenetic abnormalities, which escort to the transformation of normal cells into malignant derivatives. Despite tremendous strides have been made in the understanding of prostate cancer biology, yet approaches towards cancer-targeted therapy still face confrontations in standardization. This review brings to attention, the regulators in complex genetic backgrounds to enlighten our understanding of transformation and metastasis in human systems. Recent evidence gives a clue that prostate cancer may be linked to deregulated DNA damage repair processes, as various combinations of targeted deletions in genes controlling cell-cycle checkpoints; apoptosis and DNA repair result in prostate cancer progression and aggressiveness. An insight of the orchestration between DNA damage-based molecular responses and TRAIL provides an understanding of the mechanisms that cause apoptosis and may provide rationale for the development of novel therapeutic strategies.

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Figures

Fig. 1
Fig. 1
A diagram portraying involvement and crosstalks of ATM and DNA-PK and inter-connection with TRAIL-mediated signal transduction
Fig. 2
Fig. 2
Diagrammatic representation of the regulators involved in the induction of apoptosis and DNA damage response
Fig. 3
Fig. 3
An overview of the negative regulators of TGF signaling which are contributory in inactivation of ATM and TRAIL
See this image and copyright information in PMC

References

    1. Bhatti S, Kozlov S, Farooqi AA, Naqi A, Lavin M, Khanna KK (2011) ATM protein kinase: the linchpin of cellular defenses to stress. Cell Mol Life Sci. doi:10.1007/s00018-011-0683-9 - PMC - PubMed
    1. Farooqi AA, Fayyaz S, Bhatti S, Ismail M, Mansoor Q (2011a) Towards TRAIL to silencing of SMURF and NEDD4: FLIP is flopped. J Exp Integr Med 1:111–116
    1. Farooqi AA, Mansoor Q, Rana A, Mashhadi TM, Imran M, Naqi SA, Bhatti S (2011b) SMURF and NEDD4 interference offers therapeutic potential in chaperoning genome integrity. J Exp Integr Med 1:43–50
    1. Fayyaz S, Chaudhary S (2011) ATM: awakening the guardian angel or drugging the -absolute tailor master. J Exp Integr Med 1. doi:10.5455/jeim.300411.rw.002
    1. Fesik SW (2005) Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 5:876–885 - PubMed

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