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NBS1 (Nijmegen breakage syndrome protein 1) is a component of the MRN complex (Mre11-Rad50-Nbs1) that plays important role in detecting DNA double strand breaks (DSBs) and triggering the downstream cascade. DSBs can be caused by ionizing radiation, chemotherapy drugs, metabolic ROS, replication errors, programmed enzymatic activities during meiosis/V(D)J recombination, etc.

The TARDBP gene codes for a transcriptional repressor protein known as TDP-43. The protein encoded by the TARDBP gene binds TAR DNA and functions to regulate translation. TDP-43 can also bind RNA which leads to transcriptional repression and the formation of splice variants encoding alternate forms of proteins. Additionally, the TARDBP gene plays an important role in mRNA transport.

p62/SQSTM1 (sequestosome 1) is ubiquitously-expressed cytoplasmic/adaptor protein. SQSTM1 functions as a signaling hub for various signal transduction pathways involved in apoptosis, cell differentiation, apoptosis, immune response, and K+ channel regulation. It is conserved in vertebrates and can be induced by a wide variety of triggers including the proteasomal inhibitor PSI, PGJ2/prostaglandin J2, and the tumor promoting agent phorbol 12-myristate 13-acetate (PMA).

The extracellular matrix (ECM) is a well-structured composite of collagens, proteoglycans, glycoproteins, and growth factors proficient of generating variable measures of tissue tensile potency, from mucosal linings to bones. ECM predominantly comprises the cellular milieu outside the circulation and is established as having a major regulatory effect on cell activity.  There has been a considerable amount of attention towards the disparate conditions in which ECM unambiguously sends or alters signals to the surrounding cells.

The Lin28-Let-7 stem cell differentiation regulatory pathway is responsible for maintaining stem cell pluripotency. Specifically, Lin28 causes uridiylation of the let-7 miRNA precursor, which prevents differentiation processing by Dicer. Instead, the Uridylated let-7 is degraded by a previously unidentified exonuclease protein. In the article “A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway” HM Chang, et al.

The biological importance of protein phosphorylation is underlined by the existence of 500 or more protein kinases within the human genome. In most cases, phosphorylation of serine residues creates binding surfaces for a variety of phospho-amino acid binding proteins. Phosphorylation is a key post-translational modification necessary for normal cell signaling and is a key player in cellular function. Phosphorylated proteins mediate cell division, differentiation, signal transduction and other key cell signaling processes.

Synaptonemal Complex Protein 1 (SCP1) is a novel tumor antigen that belongs to the growing family of cancer/testis antigens (CTAs). CTAs are theoretically ideal targets for tumor immunotherapy. Unlike most auto-antigens, CTAs are highly immunogenic, even in the autologous cancer-bearing patients. Furthermore, because of their very restricted normal tissue expression, immunotherapy targeting CTAs is expected to be more specific and less toxic.

Niemann-Pick type C (NPC) disease is a severe cell lipidosis characterized by the accumulation of unesterified cholesterol in the endosomal/lysosomal system. It is a lysosomal storage disorder that affects the viscera and the central nervous system which is caused by the accumulation of cholesterol in lysosomes (1). Niemann-Pick disease type C1 has a highly variable clinical phenotype and clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia (2).

E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80) is a calcium-regulated adhesion molecule expressed in most normal epithelial tissues and the loss of E-cadherin can cause dedifferentiation and invasiveness in several cancers (1). Loss of E-Cadherin expression correlated with the invasiveness of carcinoma (2).

Integrins are a group of trans-membrane receptors which encompass alpha and beta subunits acting as adhesion particles in addition to various other important cellular functions. Integrins are recognized to enable cell-cell, cell-ECM, cell-pathogen interface along with signaling through the plasma membrane comprising of critical cellular functions such as differentiation, migration in addition to survival. Several investigators have documented variations in integrin expression and function in several cancers.