This highly acidic protein was originally studied as a putative thymic hormone because thymocyte extracts containing fragments such as thymosin alpha-1 stimulate T cells. However, this apparent function may not be physiological. The native acidic protein is expressed in a broad range of tissues, lacks a signal sequence, and is targeted to the nucleus. It is required for mitosis, although its precise role is not yet known.
Northern blot analyses using cloned prothymosin-alpha cDNA as probe revealed the presence of mRNA for this factor in the ovary (Oikawa et al., 1990).
General function
Cell organization, Cell death/survival, Anti-apoptotic, DNA Replication, Nucleic acid binding, DNA binding, Transcription factor
Comment
Jiang X, et al 2003 reported distinctive roles of PHAP proteins and prothymosin-alpha in a
death regulatory pathway.
A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was
identified by high-throughput screening as an activator of caspase-3 in extracts of a
panel of cancer cells. PETCM was used in combination with biochemical
fractionation to identify a pathway that regulates mitochondria-initiated caspase
activation. This pathway consists of tumor suppressor putative HLA-DR-associated
proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins
promoted caspase-9 activation after apoptosome formation, whereas ProT negatively
regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved
ProT inhibition and allowed apoptosome formation at a physiological concentration
of deoxyadenosine triphosphate. Elimination of ProT expression by RNA
interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated
the requirement of PETCM for caspase activation.
Inaddition, it has been proposed that Prothymosin-alpha may be involved in the remodelling of chromatin fibres through its interaction with histone H1 (Gomez-Marquez et al., 1988). Prothymosin alpha stimulates Ca2+-dependent phosphorylation of elongation factor 2 in cellular extracts (Vega et al., 1998).
Oocytes expressed ProT from primordial follicles to the eighth generation, but more developed oocytes and atretic oocytes were not immunoreactive. In hypophysectomized rats, all oocytes were immunoreactive. In hypophysectomized rats treated with follicle stimulating hormone (FSH) that promoted follicle development, the more developed oocytes did not show ProT immunoreactivity (Roson et al., 1993).