Connective Peptide

The TFCP2/Grainyhead family of transcription factors has very ancient origins; these factors can be found throughout Metazoa and in fungi. Their DNA-binding domains have a characteristic, immunoglobulin-like structure, similar to that of the well documented tumor suppressor TP53. For this reason it was proposed that they are likely to represent an ancestor of TP53. In mammals, the TFCP2/Grainyhead family consists of two distinct subfamilies. One subfamily includes the Grainyhead-like 1-3 (GRHL1-3) proteins and the other consists of TFCP2 (synonyms: CP2, LSF, LBP-1c), TFCP2L1 (synonyms: CRTR-1, LBP-9) and UBP1 (synonyms: LBP-1a, NF2d9).
The TFCP2, TFCP2L1 and UBP1 proteins are very closely related. The amino acid sequences of TFCP2 and UBP1 share 88% identity, while TFCP2 and TFCP2L1 share 70% identity. Transcription factors TFCP2 and UBP1 are ubiquitously expressed, but the expression of TFCP2L1 is tissue- and developmentally-specific, being found primarily in embryonic stem cells, adult kidneys and several other tissues. These proteins are involved in various biological phenomena, including hematopoiesis, cell cycle control, regulation of expression of immune-related genes and cytochrome P450 genes. They have also been linked to Alzheimer's disease and to the regulation of human immunodeficiency virus (HIV). In recent years there has been a considerable increase in the number of publications reporting links between transcription factors from the TFCP2/Grainyhead family and various types of cancer. TFCP2 is a pro-oncogenic factor in hepatocellular carcinoma, pancreatic cancer and breast cancer, may be important in cervical carcinogenesis and in colorectal cancer. TFCP2 can also act as a tumor suppressor, for example, it inhibits melanoma growth. Furthermore, TFCP2 is involved in epithelial-mesenchymal transition and enhances angiogenesis. TFCP2L1 maintains pluripotency and self-renewal of embryonic stem cells and was implicated in a wide variety of cancers, including clear cell renal cell carcinoma, breast cancer and thyroid cancer^[1][2][3].