Poly(ADP-ribose) polymerase 1 (PARP1) is a key molecular stress sensor and response mediator implicated in multiple cellular functions in health and diseases. Despite its importance and intrinsic involvement in pivotal molecular and cellular processes, including DNA repair, transcription regulation, chromatin organization, and cell death, the regulatory mechanisms of PARP1 are poorly understood. In this study, we show that SMURF2, a HECT-type E3 ubiquitin ligase and suggested tumor suppressor, physically interacts with PARP1 in different cellular settings, directly ubiquitinates it in vitro and stimulates its PARylation activity in cells, the phenomenon that required SMURF2 E3 ubiquitin ligase function. Intriguingly, in the cellular environment SMURF2 was found to regulate the dynamic exchange of ubiquitin moieties on PARP1, mostly decreasing its monoubiquitination. Through the set of systematic mass spectrometry analyses conducted on SMURF2-modified cells, we identified on PARP1 18 lysine residues (out of 126 present in PARP1) as sites which ubiquitination was considerably affected by SMURF2. Subsequent site-directed mutagenesis coupled with in cellula ubiquitination and PARylation assays unveiled K222 as a critical site enabling a cross talk between SMURF2-modulated monoubiquitination of PARP1 and its activity, and pointed to K498, S507, and a KTR triad (K498/K521/K524) as the main auto-PARylation sites affected by SMURF2. The results also uncovered that SMURF2 controls PARP1 interactome, influencing its functions and expression in a context-dependent manner. Taken together, these findings suggest that SMURF2-mediated ubiquitin signaling plays an essential role in PARP1 regulation, beyond the regulation of its protein expression.

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Medicinal plants are one of the nature's greatest gifts to the mankind. Each plant will have an exquisite deal of character, which can act as an antidote to various of diseases. Traditional medicine has become a vital alternative source of medicine all over the world today with some approximation of about 80% of the primary health care system in some developing countries. Medicinal plants are known to comprise of hundreds of active constituents that may be potentially useful for the development of therapeutic agents. The development of therapeutic agents involves the isolation and identification of bioactive compounds from plant materials which is crucial for drug discovery. Researchers from all around the globe have focused on drug discovery from the natures' wonder medicinal plants, forming an important group of complementary and alternative medicine (CAM) therapy. West Godavari is a part of Andhra Pradesh, India, which hosts several plants that have high therapeutic significance. Each of the plants has a unique feature which can be employed for healing of various lethal diseases. The present examination intends to review the therapeutic plant assets of West Godavari area Andhra Pradesh. This evaluation also offers the critical elements which include medicinal properties of various medicinal plants found in West Godavari district of Andhra Pradesh, India. Drug Discovery -Concepts to Market 102 Drug Discovery -Concepts to Market 104 Drug Discovery -Concepts to Market 106 Drug Discovery -Concepts to Market 110 2.18.1. Scientific evidences This plant is verified to have anticarcinogenic and anti-lipid peroxidative [181], anti-inflammatory and analgesic [182], in vitro antioxidant [183], anticancer activity [184], and in vitro anthelmintic activity [185]. Tectona grandisT. grandis Linn. belongs to family Verbenaceae is one of the most well-known timbers in the world and is famous for its dimensional stability, extreme durability, and hardness which also resists decay even when unprotected by paints and preservatives. This plant is commonly called as teak. It is one of the most famous heartwood of the world. Timber value of teak has been well-known for decades [186,187]. Scientific evidencesThis plant is verified to have hair growth activity [188], cytotoxic activity [189], anti-hemolytic anemia activity [190], hypoglycemic activity [191], anti-inflammatory activity [192], diuretic activity [193], and gastroprotective activity [194]. Tamarindus indica L.Tamarindus indica or tamarind regarded as a tropical fruit tree native to the African savannahs and it is found in numerous tropical nations. It is arranged as a monospecific class in the group of Leguminosae. The sweet and harsh taste of its natural product mash is utilized to add flavor to neighborhood cooking styles. Other than culinary, tamarind is likewise utilized as a part of the conventional drug as purgative, diuretic, antibacterial operators and also in the treatment of fever and malarial contaminations [195,196]. Scientific evidencesThis plant is verified ...

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