Poly physiological functions

Evidence for a physiological function of /S-poly(L-ma-late) is available for plasmodia of P. polycephalum. The... 

Since the discovery of poly(ADP-ribose) synthetase and its role in cellular NAD turnover there has been a great deal of speculation concerning the physiological function of this enzyme and the polymer it synthesizes. The observation that the poly(ADP-ribose) synthetase is responsible for modification of chromatin-associated proteins led to the suggestion of its involvement in regulation of nuclear metabolism. Correlations between synthesis of poly(ADP-ribose) and DNA repair, cellular differentiation, DNA synthesis, and cellular proliferation have been noted. In most of these instances, however, when one set of data... 

Inhibitors of poly(ADP-ribose) synthetase, in particular, 3-aminobenzamide (3AB), have been extensively used to elucidate possible biological functions of poly(ADP-ribosyl)ation. Inevitably, then, inhibitors occupy a prominent place in the cytogenetic investigation reported here, and care must be exercised to ensure that the pharmacological properties of an inhibitor are not equated or confused with the physiological function of poly(ADP-ribose). In this chapter, we will review the cytogenetic consequences of inhibiting poly(ADP-ribose) polymerase. 

During the past several years, it has become clear that poly(ADP-ribose) synthetase has two unique features (1, 2). One is that the enzyme requires DNA for catalytic activity and another is that the enzyme is subjected to automodification during the reaction. These two unique features wUl provide us with a key for clarifying the physiological function of this enzyme in vivo. In this article, we wLU present our recent data on molecular cloning of human poly(ADP-ribose) synthetase and will discuss the physiological functions of this enzyme on the basis of its structural characteristics. 

At present, it is still difficult to definitely clarify the exact physiological significance of poly(ADP-ribose) synthetase in vivo. It is now clear, however, that the functions of this enzyme as determined in vitro can be divided into 3 categories as shown in Fig. 4. The first function is the reaction itself. Namely, the synthesis of poly(ADP-ribose) occurs with concomitant consumption of NAD. Whether or not poly(ADP-ribose) itself has any physiological function is still unknown. Nevertheless, the consumption of the substrate NAD will influence cell viability. 

In a considerably different application, nanofabricated polyhnide surfaces can be useful for the preparation of cell spheroids, roughly spherical masses composed of cells and associated ECM that demonstrate tissue-hhe morphological and physiological functions. Cell culture on nanostructured ffuorinated poly-imides results in fibroblast cell spheroids with a density comparable to tissue in vivo, fostering interest in their development for tissue engineering applications [90]. 

One important function of DUBs is the processing of ubiquitin or ubiquitin-like proteins to their mature forms. Ubiquitin is expressed in cells as either linear poly-ubiquitin or N-terminally fused to certain ribosomal proteins [79, 80]. These gene products are processed by DUBs to separate the ubiquitin into monomers and expose the gly-gly motif at the G-terminus. Many DUBs process linear polyubiquitin or Ub-fusion proteins in vitro, but this processing appears to take place cotransla-tionally in vivo and is extremely rapid. This makes analysis difficult and leaves unanswered the question of which DUBs actually perform this function in vivo. Multiple DUBs may be able to perform this processing at a physiologically relevant level since DUB deletions rarely shows processing defects [81]. 

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