Poly polymerase cleavage

Messmer, U.K. et al., Nitric oxide induced poly(ADP-ribose) polymerase cleavage in RAW264.7 macrophage apoptosis is blocked by Bcl-2, FEES Lett., 384, 162, 1996. 

Apoptosis (programmed cell death) is characterized by a complex series of biochemical changes that culminate in cell death without inflammation or swelling, which are signs of necrosis. Embryonic, fetal, and postnatal development involve cell death by apoptosis, which serves to eliminate excessive cell proliferation and migration. Apoptosis is initiated by a variety of external stimuli and molecular events such as oxidative stress, mitochondrial permeability transition, mitochondrial cytochrome c release, activation of caspase proteases, activation of endonucleases, transglutaminase activation, and poly(ADP-ribose) polymerase cleavage. 

Herc Z, Wang ZQ. Failure of Poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrrrsis and enhanced apoptosis. Mol Cell Biol 1999 19(7) 5124-5133. 

Over expression of tumor suppressor gene bcI-2 plays an important role in cellular resistance to apoptosis caused by various factors (77). Lin et al have shown that over expression of anti-apoptotic Bcl-2 and Bc1-Xl proteins may play a role in the development of resistance to cancer therapy 18). Functional over expression of Bcl-2 has been reported to confer an anti-apoptotic potential in a variety of cell types. The role of Bcl-2 in epithelial cell-cycle control and in interactions with other cell-cycle regulators is not clearly understood. Its expression has been correlated with the hormone- and chemo-resistant phenotype in advanced prostate cancer 19). Granville et al have shown that overexpression of Bcl-2 in HL-60 cells prevented apoptosis-related events including caspase 3 and 6 activation, poly (ADP-ribose) polymerase cleavage by photodynamic therapy (20). Over expression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. 

Rosemary Phytopolyphenols Cause Cleavage of Poly-Polymerase and DFF45/ICAD... 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

In vitro experiments show that correct modification of the 3 -end requires at least three protein factors the CPSF protein, the poly-A polymerase and the poly-A binding protein. The CPSF protein (CPSF cleavage and polyadenylation specificity factor) binds to the AAUAA signal and brings the poly-A polymerase to the polyadenylation site. The poly-A polymerase is supported by the poly-A binding protein. The latter binds to the poly-A sequence and is required for the transition from the phase of synthesis of short poly-A sequences to the formation of mature poly-A sequences (ca. 200 A-residues). 

The poly(A) tail is added in a multistep process. The transcript is extended beyond the site where the poly(A) tail is to be added, then is cleaved at the poly(A) addition site by an endonuclease component of a large enzyme complex, again associated with the CTD of RNA polymerase II (Fig. 26-17). The mRNA site where cleavage occurs is marked by two sequence elements the highly conserved sequence (5 )AAUAAA(3 ), 10 to 30... 

Kaufmann, S.H., Desnoyers, S., Ottaviano, Y., Davidson, N.E. and Poirier, G.G. (1991) Specific proteolytic cleavage of poly (ADP-ribose) polymerase an early marker of chemotherapy-induced apoptosis. Cancer Res., 53, 3976-3985. 

Piot, C.A., Martini, J.F., Bui, S.K., and Wolfe, C.L. 1999. Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo. Cardiovasc. Res. 44 536-542. 

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