Is PARP1 a Hero or Villain?

PARP1 as a Hero vs Villain
Not counting histones, PARP1 [Poly(ADP-ribose) Polymerase 1] is the most abundant nuclear protein in mammalian cells. While principally known for its role in various types of DNA repair, recent work expanded it’s repertoire to include genome stability maintenance, chromatin remodeling, DNA methylation/gene expression, cellular differentiation, and cell survival modulation via NAD+/ATP regulation.1 It performs Poly(ADP-ribosyl)ation
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Advancements in The Ongoing Puzzle to Understand c-SRC

Ongoing Puzzle of c-SRC in Cancer Treatment
Nearly a half-century ago, sequences from the Rous Sarcoma Virus were used to identify the first proto-oncogene and the first of a family of non-receptor tyrosine kinases: c-SRC. Unlike its viral counterpart (v-SRC), c-SRC exists in both an active and inactive state. It is produced in almost every cell type, but expressed highest in the
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The Challenging Search for BTK Inhibitors

BTK's Involved in Systemic lupus erythematosus
Bruton’s Tyrosine Kinase (BTK) is a 76kDa non-receptor Tec kinase that plays numerous diverse roles in B-cell development, immunity, autoimmunity, infection, and cancer. From stem to stern, it consists of an N-terminal plekstrin homology (PH) domain, a TEC homology (TH) domain, two SRC homology (SH2 and SH3) domains, and a C-terminal kinase domain. Unlike SRC,
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SARM1 Forefronts Research into Major Neurological Diseases

SARM1 Causes Axonal Death
SARM1 [Sterile alpha & toll/interleukin receptor (TIR) motif-containing protein 1] consists of a N-terminal mitochondrial localization sequence (NLS), an autoinhibitory HEAT/armadillo (ARM) domain, two tandem sterile alpha motif domains (SAMs), and a C-terminal toll/interleukin receptor domain (TIR). It is a human toll like receptor (TLR) adaptor protein. TLR adaptors (MYD88, MAL, TRIF, & TRAM) usually
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SIRT2 Isoforms in Neurodegenerative Diseases & Cancer

SIRT2 Affects Neurodegenerative Diseases
Silent information regulator type 2 (Sirtuin 2 or SIRT2) is a highly evolutionarily conserved NAD+ dependent deacetylase. SIRT2 is the only Sirtuin that acts in the cytosol. It expresses in almost all tissues, but most abundantly in the central nervous system. While SIRT2 is classified as a type III histone deacetylase, it is also capable
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Can WRN Helicase Inhibitors Treat MSI-H Cancers?

Patient With WRN Helicase Syndrome
Over 100 years ago, Otto Werner first characterized a recessive autosomal disorder that caused premature, but largely typical, aging in adults, starting by the 3rd decade and resulting in death by the 6th decade via myocardial infarction or cancer. This disease, now known as Werner syndrome, is caused by specific alterations in the 162 KDa
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NSP16 Shows Promise for Anti-Viral Therapeutics

NSP16 Target for COVID-19 Therapeutics
SARS-CoV-2 virus (Covid-19) possesses one of the largest genomes of any RNA virus. While it naturally encodes structural proteins among its 29 genes, it also produces non-structural proteins that are necessary to perpetuate infection. Non-structural protein 16 (NSP16) is one such protein.1 NSP16 Camouflages Viral mRNA NSP16 is an m7GpppA-specific, S-adenosyl-L-methionine-dependent 2’-O-methyltransferase (2’-O-MTase) that “caps”
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Looking Ahead: POLQ in the Future of Immuno-Oncology

POLQ Involved in DNA Repair
The most well-known and widely studied mechanisms of double-stranded DNA break (DSB) repairs are homologous recombination (HR) and classical non-homologous end joining (C-NHEJ). HR is almost error-free due to formatting by the homologous sister chromosome. C-NHEJ relies on direct ligation of double-stranded DNA ends and only ever presents errors at the junction points. Recently, a
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Discovering the Emerging Importance of PARG in Immunity

PARG in Human Immunity
Poly (ADP-ribose) glycohydrolase (PARG), along with poly (ADP-ribose) polymerase 1 (PARP1) are the principal elements of the DNA damage response (DDR). When single-strand breaks occur in cellular DNA, PARP1 mediates the poly ADP ribosylation of itself and target proteins, such as histones, promoting the decompaction of chromatin and recruiting relevant enzymes to initiate DNA repair.
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Helicases as Powerful Tools in Innate Immunity

Helicases Used in Innate Immunity
Helicases are among the largest and most highly conserved families of enzymatic proteins in eukaryotic organisms. These proteins utilize NTP hydrolysis (usually ATP) to drive their recognition, remodeling, and response to target DNA or RNA.1 Nearly every aspect of nucleic acid metabolism is mediated by helicases. DNA helicases function in replication, repair, recombination, transcription, chromosome
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