The transcription factor TFIIA is encoded by two genes, TFIIAαβ and TFIIAγ. In higher eukaryotes, the TFIIAαβ is translated as a precursor and undergoes proteolytic cleavage; the regulation and biological implications of the cleavage have remained elusive. We determined by Edman degradation that the TFIIAβ subunit starts at Asp 278. We found that a cleavage recognition site (CRS), a string of amino acids QVDG at positions −6 to −3 from Asp 278, is essential for cleavage. Mutations in the CRS that prevent cleavage significantly prolong the half‐life of TFIIA. Consistently, the cleaved TFIIA is a substrate for the ubiquitin pathway and proteasome‐mediated degradation. We show that mutations in the putative phosphorylation sites of TFIIAβ greatly affect degradation of the β‐subunit. We propose that cleavage and subsequent degradation fine‐tune the amount of TFIIA in the cell and consequently the level of transcription.