TY - JOUR
T1 - PARP-1 cleavage fragments
T2 - Signatures of cell-death proteases in neurodegeneration
AU - Chaitanya, Ganta Vijay
AU - Alexander, Jonathan S.
AU - Babu, Phanithi Prakash
N1 - Funding Information:
Subba Rao, INSA Senior Scientist, JNTU, Hyderabad, India for critical suggestions. Post-doctoral fellowship from the Malcolm Feist Cardiovascular Research Endowment-LSU Health Sciences Center-Shreveport to Ganta Vijay Chaitanya is acknowledged. Funding from DBT, DST and ICMR, New Delhi, Government of India to Prof. Prakash Babu is acknowledged.
PY - 2010
Y1 - 2010
N2 - The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine repair of DNA damage by adding poly (ADP ribose) polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs)) on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.
AB - The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine repair of DNA damage by adding poly (ADP ribose) polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs)) on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.
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U2 - 10.1186/1478-811X-8-31
DO - 10.1186/1478-811X-8-31
M3 - Review article
C2 - 21176168
AN - SCOPUS:84858169363
SN - 1478-811X
VL - 8
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
M1 - 31
ER -