Cell Proliferation

By Jamshed Arslan, Pharm D, PhD

YAP1 (Yes-associated protein 1) is a  transcriptional co-activator which acts as a major effector of Hippo signaling pathway that regulates organ size/ tissue homeostasis and cell proliferation, and is an established oncogene (1).  Hippo signaling activation results in the phosphorylation mediated inactivation of YAP1, and restriction of YAP1’s transcriptional activity is the principal mechanism of growth and tumor suppression by Hippo pathway.

The thymidine analogue bromodeoxyuridine (BrdU) has a long, colorful history of heavy use in molecular and cytokinetic studies (1, 2). BrDU is incorporated into newly synthesized DNA only in S-phase cells, and then immunocytochemically detected with BrDU antibodies. This method allows for extremely accurate and comprehensive comparative studies of a variety of cells ranging from normal to neoplastic.

Proliferating cell nuclear antigen (PCNA) is an evolutionarily well-conserved protein found in all eukaryotic species as well as in Archaea. PCNA was first shown to be involved in DNA replication. However PCNA functions are associated with other vital cellular processes such as chromatin remodeling, DNA repair, sister-chromatid cohesion and cell cycle control as well (1).

Nucleolin is a multifunctional phosphoprotein ubiquitously distributed in the nucleolus, nucleus and cytoplasm of the cell. Nucleolin has a bipartite nuclear localization signal sequence and is conserved across the species. Nucleolin levels are expressed in abundance in exponentially growing cells and it regulates various aspects of DNA and RNA metabolism, chromatin structure, rDNA transcription, rRNA maturation, cytokinesis, nucleogenesis, cell proliferation and growth (1).