Recombinant Human ALDH1A2 His-tag, CF

Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that detoxify aldehydes by oxidizing them to carboxylic acids. Nineteen ALDHs are present in humans, expressed in a variety of organelles and having different substrate preferences (1). Human ALDH1A2 is a NAD-dependent, cytosolic member of the ALDH1A subfamily class 1 that forms active tetramers that synthesize retinoic acid from retinal.  Each monomer has three functional regions: a catalytic domain containing the active site cysteine, an NAD-binding domain, and the oligomerization domain (2, 3). ALDH1A2 exhibits the highest substrate specificity and catalytic efficiency for retinal oxidation to retinoic acid (RA) (4) and thus plays an important role in regulation of RA production and signaling. ALDH1A2 null mice are embryonic lethal (5) and mutations in ALDH1A2 are associated with pathological conditions such as osteoarthris (6-8). Additionally, ALDH1A2 is suggested to play a role in several cancers. ALDH1A2 was a suggested tumor marker (9, 10) and predictor of prostate cancer relapse (11). Abnormally low levels of ALDH1A2 has been observed in several cancers including breast (12), squamous cell carcinoma of the head and neck (13), and specifically in high grade ovarian cancer, suggesting high expression may be associated with favorable prognosis (14).  Overexpression of ALDH1A2 in cancer lines resulted in decreased proliferation and migration (14) supporting that ALDH1A2 plays a tumor suppressor role. In contrast, ALDH1A2 is reported to exhibit high expression correlated with worse overall survival in non-small-cell lung cancer (15) and chemoresistant cancer stem cells in neuroblastoma (16, 17). Pharmacologically specific inhibitors and activators of ALDH1A2 are of interest due to its implied role in a variety of diseases and proliferation and drug resistance (1, 3, 15, 18).