In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by CHEK2 gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded CHEK2 protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in CHEK2s gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene.
Neural cell adhesion molecule L1-like protein, also known as close homolog of L1 (CHL1) is the prototypic member of the CTF / NF-1 family of transcription factors that serve as a novel calcium signaling pathway-responsive transcription factor and is considered as a member of the largest ctf complementation group, consisting of 30 of 126 ctf mutants isolated. CHL1 is a cell adhesion molecule highly related to L1. It contains structure plan of six extracellular C2-type immunoglobulin (Ig) domains followed by five fibronectin typeⅢ domains linked by a single membrane-spanning region to a short cytoplasmic domain. The extracellular portion of CHL1 is higyly glycosylated and involved them in hemophilic disease.
Mouse Chordin-Like 2, also known as CHL2, is a novel chordin family member with structural homology to CHL1 which is implicated in tumor angiogenesis. The mouse CHL2 gene encodes a 426 amino acids (aa) protein with a 25 aa signal peptide. The mature chain of CHL2 protein contains two potential N-linked glycosylation sites, one putative NLS and three 63 aa cysteine-rich von Willebrand type C repeats (CRs). CHL2 gene is weakly expressed in the liver and kidney, partly expressed in the connective tissues of reproductive organs such as ligaments of the ovary and oviduct in females, and of testis, epididymis and certain male accessory sex glands in males. Recombinant mCHL2 protein interacted directly with five BMPs and one GDF thereby inhibiting, in vitro, several BMP/GDF-dependent processes including, osteogenic differentiation of C2C12 mesenchymal progenitor cells by several BMPs, ATDC5 embryonal carcinoma cells by GDF5 and BMP4-dependent lymphohematopoietic (CD34+CD31hi and CD34+CD31lo) progenitor cell development from ES cells. CHL2 may inhibits BMPs activity by blocking their interaction with their receptors, and has a negative regulator effect on the cartilage formation/regeneration from immature mesenchymal cells, by preventing or reducing the rate of matrix accumulation. Also, it may play a role during myoblast and osteoblast differentiation, and maturation.
Pancreastatin: Strongly inhibits glucose induced insulin release from the pancreas.Catestatin: Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Can induce mast cell migration, degranulation and production of cytokines and chemokines.Serpinin: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation . Pyroglutaminated (pGlu)-serpinin exerts an antiapoptotic effect on cells exposed to oxidative stress .
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