The Prokineticins: A NOVEL PAIR OF REGULATORY PEPTIDES

Transcriptional regulation of prokineticin 2. The promoter of the PK2-encoding gene, in both human and mouse, contains multiple E-box sequences (CACGTG) that are targeted by basic helix-loop-helix (bHLH) transcription factors (ovals; CLOCK/BMAL1 and Ngn1/MASH1 dimers are schematized here). The expression of PK2 (orange) is a common functional target for both sets of transcriptional factors, although distinct biological processes are ultimately affected, depending the particular transcriptional machinery that is recruited (indicated by different shades of blue arrows). PK2 is also induced by hypoxia (as is PK1), and thus HIF-1 (hypoxia-inducing factor, also a bHLH transcription factor) may also regulate the functionality of PK2. (The dashed outline around Ngn1 is intended to indicate the speculative nature of its specific transcriptional role in this instance. See text for details.)